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1.  A Model for the Roll-Out of Comprehensive Adult Male Circumcision Services in African Low-Income Settings of High HIV Incidence: The ANRS 12126 Bophelo Pele Project 
PLoS Medicine  2010;7(7):e1000309.
Bertrand Auvert and colleagues describe the large-scale roll-out of adult male circumcision through a program in South Africa.
Background
World Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting.
Methods and Findings
The ANRS 12126 “Bophelo Pele” project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project's main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing.
Conclusion
This study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed about 25 million people since 1981, and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV infection is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having one or a few partners, and by always using a male or female condom. In addition, three trials in sub-Saharan Africa recently reported that medicalized adult male circumcision (AMC)—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce HIV transmission rates in men by more than a half. Thus, AMC delivered as a catch-up campaign—in the long-term, circumcision of male infants is likely to be a more sustainable strategy—has the potential to reduce the prevalence of HIV (the proportion of the population infected with HIV) in sub-Saharan Africa.
Why Was This Study Done?
The World Health Organization (WHO) and the Joint United Nations Programme on AIDS (UNAIDS) now recommend that AMC programs should be rolled-out wherever there is a generalized HIV epidemic and few men are circumcised. Accordingly, these organizations have defined a minimum package of AMC services and have issued guidelines and tools designed to engage communities in the roll-out and to ensure that appropriate AMC counseling and surgical facilities are available. But is rapid AMC roll-out feasible in real-life settings? Here, the researchers try to find out by studying the “Bophelo Pele” (Health First) project. This project, which follows the WHO/UNAIDS guidelines for AMC, aims to offer free, safe AMC services to all men aged 15 years or more living in the Orange Farm township in South Africa as part of a community-based intervention against HIV. Orange Farm is in a low-income region of South Africa where HIV prevalence is 15.2% and AMC prevalence is about 25%.
What Did the Researchers Do and Find?
Before the Bophelo Pele project started in January 2008, the researchers consulted the community about the implementation of AMC, helped to create a community advisory board, organized community workshops to discuss the project, and surveyed people's knowledge about AMC and willingness to undergo AMC. These activities indicated a high level of community support for the project and a high level of willingness among men to undergo AMC. Once the project started, the researchers used multiple communication channels to tell the Orange Farm residents about AMC and broader HIV prevention strategies and provided eligible men with counseling about AMC and with voluntary HIV counseling and testing during the recruitment process. Three days after recruitment, eligible men were circumcised free-of-charge at the project's main center, where three teams of one medical circumciser and five nurses were able to complete up to 150 AMCs per day. By November 2009, 14,011 men had been circumcised (more than a third of the eligible men in the township), and AMC uptake was still increasing steadily. Nearly all the men circumcised over one 2-month period rated the AMC services positively in a survey and adverse effects (all mild) occurred after fewer than 1 in 50 circumcisions.
What Do These Findings Mean?
These findings suggest that the rapid roll-out of high-quality, free AMC as an intervention against HIV has been successful in the Orange Farm township. However, other findings highlight some of the challenges that face AMC roll-out. For example, only a quarter of the participants agreed to voluntary HIV counseling and testing, which is worrying because newly circumcised HIV-positive men have an increased risk of transmitting HIV if they resume sexual activity too soon after the operation. Similarly, only two-thirds of the participants returned for a check-up after circumcision; this proportion needs to be increased to ensure the safety and efficacy of AMC programs. Nevertheless, these findings and those from similar intervention programs in Kenya and Uganda indicate that AMC scale-up should be feasible, at least in the short term, as an HIV prevention strategy in low-income communities where there is a high HIV prevalence and a low AMC rate.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000309.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, and on circumcision and HIV (in English and Spanish)
More information about male circumcision is available from WHO and from the Clearinghouse on Male Circumcision, including a June 2010 report from WHO/UNAIDS entitled Progress in male circumcision scale-up: country implementation and research update
More information about the Bophelo Pele project is available
doi:10.1371/journal.pmed.1000309
PMCID: PMC2907271  PMID: 20652013
2.  Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study 
PLoS Medicine  2015;12(9):e1001873.
Background
Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.
Methods and Findings
Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample.
Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1–12, with adolescents (16–19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159–426). HIVST uptake in months 13–24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%–7.8%) positive participants. Being “forced to test”, usually by a main partner, was reported by 2.9% (95% CI 2.6%–3.2%) of 10,017 questionnaire respondents in months 1–12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%–97.0%) and a specificity of 99.9% (95% CI 99.6%–100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover.
Conclusions
Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.
In a prospective study, Augustine Choko and colleagues assess uptake, accuracy, and outcomes of implementation of community-wide HIV self-testing delivered and supported by resident community volunteers in 14 neighborhoods of Blantyre, Malawi.
Editors' Summary
Background
Every year, about 2.1 million people (70% of whom live in sub-Saharan Africa) are newly infected with HIV, the virus that causes AIDS, and 1.5 million people (again, mainly in sub-Saharan Africa) die as a result. HIV, which is usually transmitted through unprotected sex with an infected individual, gradually destroys CD4 lymphocytes and other immune system cells, leaving HIV-positive individuals susceptible to other serious infections and to unusual cancers. HIV is diagnosed by looking for antibodies to HIV in blood or saliva. After diagnosis, the progression of HIV infection is monitored by regularly counting the number of CD4 cells in the blood. Initiation of antiretroviral therapy—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual’s CD4 count falls below 500 cells/μl or when he or she develops an AIDS-defining condition.
Why Was This Study Done?
HIV-positive individuals need to know their status so that they can take steps to avoid transmitting the virus to other people (for example, by always using a condom during sexual intercourse) and so that they can begin treatment. Treatment helps to keep HIV-positive individuals healthy but also reduces their chances of transmitting the virus to their sexual partners. Unfortunately, many HIV-positive individuals are unaware of their status. The situation is particularly bad in sub-Saharan Africa, where, despite major investments in facility-based and community-based HIV testing and counseling (HTC) programs, only a quarter of adults have had a recent HIV test, and only half of the people living with HIV know they are HIV positive. Barriers to facility-based HTC include concern about lack of confidentiality and fears of stigmatization. Home-based HTC avoids some of these barriers and can achieve high uptake of testing, but doubts have been expressed about the sustainability of this approach to testing. Here, the researchers evaluate an alternative to home-based HTC—HIV self-testing (HIVST)—by undertaking a community-based prospective study of HIVST in Blantyre, Malawi. HIVST involves individuals performing and interpreting their own HIV test and has the potential to be widely implemented with minimal involvement of trained healthcare workers.
What Did the Researchers Do and Find?
Trained resident volunteer-counselors offered one oral HIVST kit (a kit that measures HIV in saliva) per year for a two-year period to 16,660 adult residents in 14 neighborhoods in urban Blantyre. All the participants received instructions on how to use the kits, pre- and post-counseling, and, for participants self-testing HIV positive, a referral card to attend an HIV care clinic. The residents also completed a questionnaire about their experience of HIVST. Three-quarters of the residents self-tested in the first and second year of the study. HIVST uptake was more rapid in the second year than in the first year and was high among men and adolescents, two hard-to-reach populations. Three-quarters of the residents who self-tested during the first year of the study shared their results with a volunteer-counselor. Of the 1,257 participants who discovered they were HIV positive during the first year of the study, more than half accessed HIV care. Importantly, 94.4% of the participants reported that they were happy with HIVST even though 2.9% reported being forced to take the test, usually by a main partner; no HIVST-related partner violence or suicides were reported by the study’s community surveillance system. Finally, HIVST and repeat HTC results agreed in 99.4% of participants selected as a quality assurance sample (one in 20 of the participants).
What Do These Findings Mean?
These findings show that, in urban neighborhoods in Malawi, coverage with community-based HIVST was high (particularly among adolescents and men) in two successive years and that HIVST was safe, accurate, and acceptable. Importantly, HIVST using a delivery model based on trained volunteers led to acceptable linkage into HIV care services, and the approach had a very low incidence of major social harms such as partner violence. Uncertainty about estimates of uptake and linkage to care and other aspects of the study design may limit the accuracy of these results. Nevertheless, these findings suggest that scaling up HIVST could complement existing strategies for providing early HIV diagnosis and periodic repeat testing and could thus have a sustained impact on the coverage of HIV testing and care in Africa and on the control of the HIV/AIDS epidemic.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001873.
Information is available from the US National Institute of Allergy and Infectious Diseases on all aspects of HIV infection and AIDS, including testing and diagnosis
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV testing, HIV/AIDS treatment and care, and HIV prevention, and on HIV/AIDS in Malawi and in sub-Saharan Africa; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its new consolidated guidelines on HIV testing
The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it; UNAIDS also provides detailed region-specific information and policy news.
doi:10.1371/journal.pmed.1001873
PMCID: PMC4562710  PMID: 26348035
3.  Mass HIV Treatment and Sex Disparities in Life Expectancy: Demographic Surveillance in Rural South Africa 
PLoS Medicine  2015;12(11):e1001905.
Background
Women have better patient outcomes in HIV care and treatment than men in sub-Saharan Africa. We assessed—at the population level—whether and to what extent mass HIV treatment is associated with changes in sex disparities in adult life expectancy, a summary metric of survival capturing mortality across the full cascade of HIV care. We also determined sex-specific trends in HIV mortality and the distribution of HIV-related deaths in men and women prior to and at each stage of the clinical cascade.
Methods and Findings
Data were collected on all deaths occurring from 2001 to 2011 in a large population-based surveillance cohort (52,964 women and 45,688 men, ages 15 y and older) in rural KwaZulu-Natal, South Africa. Cause of death was ascertained by verbal autopsy (93% response rate). Demographic data were linked at the individual level to clinical records from the public sector HIV treatment and care program that serves the region. Annual rates of HIV-related mortality were assessed for men and women separately, and female-to-male rate ratios were estimated in exponential hazard models. Sex-specific trends in adult life expectancy and HIV-cause-deleted adult life expectancy were calculated. The proportions of HIV deaths that accrued to men and women at different stages in the HIV cascade of care were estimated annually.
Following the beginning of HIV treatment scale-up in 2004, HIV mortality declined among both men and women. Female adult life expectancy increased from 51.3 y (95% CI 49.7, 52.8) in 2003 to 64.5 y (95% CI 62.7, 66.4) in 2011, a gain of 13.2 y. Male adult life expectancy increased from 46.9 y (95% CI 45.6, 48.2) in 2003 to 55.9 y (95% CI 54.3, 57.5) in 2011, a gain of 9.0 y. The gap between female and male adult life expectancy doubled, from 4.4 y in 2003 to 8.6 y in 2011, a difference of 4.3 y (95% CI 0.9, 7.6). For women, HIV mortality declined from 1.60 deaths per 100 person-years (95% CI 1.46, 1.75) in 2003 to 0.56 per 100 person-years (95% CI 0.48, 0.65) in 2011. For men, HIV-related mortality declined from 1.71 per 100 person-years (95% CI 1.55, 1.88) to 0.76 per 100 person-years (95% CI 0.67, 0.87) in the same period. The female-to-male rate ratio for HIV mortality declined from 0.93 (95% CI 0.82–1.07) in 2003 to 0.73 (95% CI 0.60–0.89) in 2011, a statistically significant decline (p = 0.046). In 2011, 57% and 41% of HIV-related deaths occurred among men and women, respectively, who had never sought care for HIV in spite of the widespread availability of free HIV treatment. The results presented here come from a poor rural setting in southern Africa with high HIV prevalence and high HIV treatment coverage; broader generalizability is unknown. Additionally, factors other than HIV treatment scale-up may have influenced population mortality trends.
Conclusions
Mass HIV treatment has been accompanied by faster declines in HIV mortality among women than men and a growing female–male disparity in adult life expectancy at the population level. In 2011, over half of male HIV deaths occurred in men who had never sought clinical HIV care. Interventions to increase HIV testing and linkage to care among men are urgently needed.
Jacob Bor and colleagues use demographic data from a longitudinal surveillance cohort to identify increased gains in life expectancy among women compared to men in the years following antiretroviral therapy scale-up in rural South Africa.
Editors' Summary
Background.
AIDS has killed 39 million people over the past three decades, and about 35 million people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the retrovirus that causes AIDS. HIV destroys immune system cells, leaving HIV-positive individuals susceptible to other serious infections. Early in the AIDS epidemic, most HIV-positive individuals died within ten years of infection. Then, in 1996, effective antiretroviral therapy (ART) became available. For people living in high-income countries, HIV infection became a chronic condition, but HIV/AIDS remained largely untreated and fatal in resource-limited countries. In 2003, the international community began to work towards achieving universal access to ART. Now, at least a third of people living with HIV have access to ART, the global rate of AIDS-related deaths has fallen by more than a third from its 2005 peak, and the life expectancy (how long a person is likely to live based on their year of their birth, their current age, and other demographic factors) of HIV-positive adults has markedly increased.
Why Was This Study Done?
Although ART has been provided without charge to patients in South African public clinics since 2004, HIV/AIDS remains the leading cause of death in many parts of South Africa. Reducing the lingering burden of HIV mortality is a policy priority. Prior studies have found worse outcomes among men in HIV care and treatment. Here, the researchers assess the evolution of sex disparities in life expectancy and HIV mortality rates at the population level with the scale-up of ART in a rural region of KwaZulu-Natal, South Africa, where 29% of the population is HIV-positive. Different trends in life expectancy for men and women following ART scale-up may reflect differences in the underlying burden of HIV disease—women tend to be infected and die at younger ages—as well as differences in access to HIV testing, care, and treatment. The researchers also assess where in the cascade of HIV care and treatment HIV mortality occurs for men and women. Knowing more about sex-specific trends in population life expectancy and where the lingering burden of HIV mortality occurs could help experts design strategies to further reduce HIV mortality in regions where free ART is widely available.
What Did the Researchers Do and Find?
The researchers linked demographic data obtained through regular household surveys, including all deaths occurring between 2001 and 2011, for nearly 100,000 adults living in rural KwaZulu-Natal to clinical records held by the public sector HIV treatment and care program. In addition, trained nurses visited households where there had been a death and collected data that were used to determine the probable cause of death (verbal autopsy). Analysis of these data indicated that, between 2003 and 2011, female adult life expectancy increased by 13.2 years (from 51.3 years to 64.5 years), whereas male life expectancy increased by only 9 years (from 46.9 years to 55.9 years). Thus, the gap between female and male adult life expectancy doubled between 2003 and 2011. Moreover, although HIV-related mortality among women and men was similar in 2003, in 2011 women were 27% less likely to die from HIV than men. With the scale-up of ART, male sex has emerged as a risk factor for HIV mortality at the population level. Finally, in 2011, 55% of all male HIV-related deaths and 40% of all female HIV-related deaths occurred among men and women who had never sought care for HIV/AIDS.
What Do These Findings Mean?
These findings suggest that although the mass provision of free ART in South Africa has coincided with a reduction in HIV-related mortality among both men and women, ART scale-up has been accompanied by faster declines in HIV-related deaths among women than men and by a growing female–male disparity in adult life expectancy. Notably, these findings also indicate that despite the wide availability of ART, about half of all HIV-related deaths in the study population occurred among people who had never sought care for HIV. The use of verbal autopsy to determine the probable cause of death may limit the accuracy of these findings, and factors other than the scale-up of ART may have influenced the population mortality trends. Moreover, these findings may not be generalizable to other populations. However, these results highlight the need for further research to understand why men are not as likely as women to seek and adhere to HIV care and treatment, and to design effective interventions to increase the uptake of HIV services among men. Without better outreach to men, the researchers conclude, the full benefits of mass ART provision will not be realized.
Additional Information.
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001905.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART and on HIV/AIDS in South Africa; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization (WHO) provides information on all aspects of HIV/AIDS (in several languages), including its Consolidated Guidelines on the Use of Antiretroviral Therapy for Treating and Preventing HIV Infection and information on the WHO/UNAIDS Treatment 2.0 strategy, an initiative to expand access to HIV testing and ART
The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy; UNAIDS also provides detailed information about HIV/AIDS in South Africa
More information about the population-based surveillance cohort that provided the data for this study is available from the Africa Centre for Population Health website
doi:10.1371/journal.pmed.1001905
PMCID: PMC4658174  PMID: 26599699
4.  Home-Based Versus Mobile Clinic HIV Testing and Counseling in Rural Lesotho: A Cluster-Randomized Trial 
PLoS Medicine  2014;11(12):e1001768.
Niklaus Labhardt and colleagues investigate how different HIV testing and counseling strategies, based on home visits or mobile clinics, reach different populations in a rural African setting.
Please see later in the article for the Editors' Summary
Background
The success of HIV programs relies on widely accessible HIV testing and counseling (HTC) services at health facilities as well as in the community. Home-based HTC (HB-HTC) is a popular community-based approach to reach persons who do not test at health facilities. Data comparing HB-HTC to other community-based HTC approaches are very limited. This trial compares HB-HTC to mobile clinic HTC (MC-HTC).
Methods and Findings
The trial was powered to test the hypothesis of higher HTC uptake in HB-HTC campaigns than in MC-HTC campaigns. Twelve clusters were randomly allocated to HB-HTC or MC-HTC. The six clusters in the HB-HTC group received 30 1-d multi-disease campaigns (five villages per cluster) that delivered services by going door-to-door, whereas the six clusters in MC-HTC group received campaigns involving community gatherings in the 30 villages with subsequent service provision in mobile clinics. Time allocation and human resources were standardized and equal in both groups. All individuals accessing the campaigns with unknown HIV status or whose last HIV test was >12 wk ago and was negative were eligible. All outcomes were assessed at the individual level. Statistical analysis used multivariable logistic regression. Odds ratios and p-values were adjusted for gender, age, and cluster effect.
Out of 3,197 participants from the 12 clusters, 2,563 (80.2%) were eligible (HB-HTC: 1,171; MC-HTC: 1,392). The results for the primary outcomes were as follows. Overall HTC uptake was higher in the HB-HTC group than in the MC-HTC group (92.5% versus 86.7%; adjusted odds ratio [aOR]: 2.06; 95% CI: 1.18–3.60; p = 0. 011). Among adolescents and adults ≥12 y, HTC uptake did not differ significantly between the two groups; however, in children <12 y, HTC uptake was higher in the HB-HTC arm (87.5% versus 58.7%; aOR: 4.91; 95% CI: 2.41–10.0; p<0.001). Out of those who took up HTC, 114 (4.9%) tested HIV-positive, 39 (3.6%) in the HB-HTC arm and 75 (6.2%) in the MC-HTC arm (aOR: 0.64; 95% CI: 0.48–0.86; p = 0.002). Ten (25.6%) and 19 (25.3%) individuals in the HB-HTC and in the MC-HTC arms, respectively, linked to HIV care within 1 mo after testing positive. Findings for secondary outcomes were as follows: HB-HTC reached more first-time testers, particularly among adolescents and young adults, and had a higher proportion of men among participants. However, after adjusting for clustering, the difference in male participation was not significant anymore.
Age distribution among participants and immunological and clinical stages among persons newly diagnosed HIV-positive did not differ significantly between the two groups. Major study limitations included the campaigns' restriction to weekdays and a relatively low HIV prevalence among participants, the latter indicating that both arms may have reached an underexposed population.
Conclusions
This study demonstrates that both HB-HTC and MC-HTC can achieve high uptake of HTC. The choice between these two community-based strategies will depend on the objective of the activity: HB-HTC was better in reaching children, individuals who had never tested before, and men, while MC-HTC detected more new HIV infections. The low rate of linkage to care after a positive HIV test warrants future consideration of combining community-based HTC approaches with strategies to improve linkage to care for persons who test HIV-positive.
Trial registration
ClinicalTrials.gov NCT01459120
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Annually, about 2.3 million people become newly infected with HIV, the virus that causes AIDS by gradually destroying CD4 cells and other immune system cells, thereby leaving HIV-infected individuals susceptible to other serious infections. HIV can be transmitted through unprotected sex with an infected partner, from an HIV-positive mother to her unborn child, or through the injection of drugs with shared needles. Infection with HIV is usually diagnosed by looking for antibodies to HIV in the blood or saliva. After diagnosis, the progression of HIV infection is monitored by regularly counting the number of CD4 cells in the blood. Initiation of antiretroviral therapy (ART)—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual's CD4 count falls below 500 cells/µl or when he or she develops signs of advanced or severe disease, such as unusual infections.
Why Was This Study Done?
To control HIV/AIDS, HIV transmission needs to be reduced, and ART delivery needs to be increased. In settings of high HIV prevalence, universal coverage of HIV testing and counseling (HTC) is essential if these goals are to be met. Unfortunately, many people refuse “facility-based” HTC (HTC delivered at health care facilities) because they fear stigmatization and discrimination. Moreover, many people in resource-limited settings rarely visit health care facilities. Community-based HTC may be one way to increase the uptake of HTC, particularly among populations that are hard to reach, such as men and first-time testers, but which form of community-based HTC will be most effective? In this cluster-randomized trial, the researchers ask whether home-based HTC (HB-HTC)—community-based HTC in which health care workers go door-to-door to offer HTC to people in their own home—results in a higher uptake of HTC than HTC delivered through community gatherings and mobile clinics (MC-HTC) in two rural areas in Lesotho. Nearly a quarter of adults are HIV-positive in Lesotho, but only 61% of people who need ART currently receive treatment. A cluster-randomized trial compares outcomes in groups (clusters) of people chosen at random to receive different interventions.
What Did the Researchers Do and Find?
The researchers allocated 12 clusters, each comprising a health center and its catchment area, to the HB-HTC or MC-HTC intervention. In the HB-HTC arm (1,171 participants), HTC teams going door-to-door delivered a multi-disease campaign that included HTC to five villages in each cluster. In the MC-HTC arm (1,392 participants), the multi-disease campaign was delivered at community gatherings with subsequent service provision in mobile clinics. Overall, HTC uptake was higher in the HB-HTC arm than in the MC-HTC arm (92.5% and 86.7% uptake, respectively). Among participants aged ≥12 years, there was no significant difference in HTC uptake between the arms, whereas among children aged <12 years, HTC uptake was significantly higher in the HB-HTC arm than in the MC-HTC arm (87.5% versus 58.7%; a significant difference is a difference unlikely to have happened by chance). Among individuals who took up HTC, 3.6% and 6.2% tested positive for HIV in the HB-HTC arm and MC-HTC arm, respectively. In both arms, only a quarter of individuals who tested positive accessed HIV care within a month of their positive test result. Finally, HB-HTC reached more first-time testers (particularly among adolescents) and tended to reach more men than MC-HTC.
What Do These Findings Mean?
These findings suggest that, in rural Lesotho, both HB-HTC and MC-HTC delivered as part of a multi-disease campaign can achieve a high uptake of HTC. Various aspects of the trial design (for example, the small number of clusters) may limit the accuracy of the findings reported here. Notably, however, these findings suggest that the choice between HB-HTC and MC-HTC should be guided by the objective of the HTC intervention in specific settings. Where equity of access is of concern and where increased HTC coverage, particularly among groups in which HTC coverage is generally poor (including men, first-time testers, and children), is paramount, HB-HTC may be the preferred option. By contrast, the MC-HTC approach may be more appropriate in settings where the detection of new HIV infections is the major goal. Finally, and importantly, the findings of this trial highlight the need for further research into strategies designed to improve the linkage between HIV testing and enrollment into care.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001768.
The World Health Organization provides information on all aspects of HIV/AIDS, including information on HIV counseling and testing (in several languages)
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV testing, and on HIV/AIDS in Lesotho
The UK National Health Service Choices website provides information (including personal stories) about HIV/AIDS
The “UNAIDS Report on the Global AIDS Epidemic 2013” provides up-to-date information about the AIDS epidemic and efforts to halt it
Stories about living with HIV/AIDS are available through Avert and through healthtalk.org
More information about this trial is available
doi:10.1371/journal.pmed.1001768
PMCID: PMC4267810  PMID: 25513807
5.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Background
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Conclusions
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001295.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project http://www.healthpolicyproject.com has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
doi:10.1371/journal.pmed.1001295
PMCID: PMC3424253  PMID: 22927800
6.  Towards Universal Voluntary HIV Testing and Counselling: A Systematic Review and Meta-Analysis of Community-Based Approaches 
PLoS Medicine  2013;10(8):e1001496.
In a systematic review and meta-analysis, Amitabh Suthar and colleagues describe the evidence base for different HIV testing and counseling services provided outside of health facilities.
Please see later in the article for the Editors' Summary
Background
Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC.
Methods and Findings
PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's “risk of bias” tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates.
 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27–18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06–1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16–1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37–0.96), relative to facility-based approaches. 80% (95% CI 75%–85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%–85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2–US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52–14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73–1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested.
Conclusions
Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment.
Review Registration
International Prospective Register of Systematic Reviews CRD42012002554
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Three decades into the AIDS epidemic, about 34 million people (most living in resource-limited countries) are infected with HIV, the virus that causes AIDS. Every year another 2.2 million people become infected with HIV, usually through unprotected sex with an infected partner, and about 1.7 million people die. Infection with HIV, which gradually destroys the CD4 lymphocytes and other immune system cells that provide protection from life-threatening infections, is usually diagnosed by looking for antibodies to HIV in the blood or saliva. Disease progression is subsequently monitored in HIV-positive individuals by counting the CD4 cells in their blood. Initiation of antiretroviral drug therapy—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual's CD4 count falls below 500 cells/µl of blood or when he or she develops signs of severe or advanced disease, such as unusual infections.
Why Was This Study Done?
As part of intensified efforts to eliminate HIV/AIDS, United Nations member states recently set several HIV-related targets to be achieved by 2015, including reduced transmission of HIV and increased delivery of antiretroviral therapy. These targets can only be achieved if there is a large expansion in HIV testing and counseling (HTC) and increased access to HIV prevention and care services. The World Health Organization currently recommends that everyone attending a healthcare facility in regions where there is a generalized HIV epidemic (defined as when 1% or more of the general population is HIV-positive) should be offered HTC. However, many people rarely visit healthcare facilities, and others refuse “facility-based” HTC because they fear stigmatization and discrimination. Thus, facility-based HTC alone is unlikely to be sufficient to enable national and global HIV targets to be reached. In this systematic review and meta-analysis, the researchers evaluate the performance of community-based HTC approaches such as index testing (offering HTC to the sexual and injecting partners and household members of people with HIV), mobile testing (offering HTC through a service that visits shopping centers and other public facilities), and door-to-door testing (systematically offering HTC to homes in a catchment area). A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 117 studies (most undertaken in Africa and North America) involving 864,651 participants that evaluated community-based HTC approaches. Among these studies, the percentage of people offered community-based HTC who accepted it (HTC uptake) was 88% for index testing, 87% for self-testing, 80% for door-to-door testing, 67% for workplace testing, and 62% for school-based testing. Compared to facility-based approaches, community-based approaches increased the chances of an individual's CD4 count being above 350 cells/µl at diagnosis (an important observation because early diagnosis improves subsequent outcomes) but had a lower positivity rate, possibly because people with symptoms of HIV are more likely to visit healthcare facilities than healthy individuals. Importantly, 80% of participants in the community-based HTC studies had their CD4 count measured after HIV diagnosis, and 73% of the participants initiated antiretroviral therapy after their CD4 count fell below national eligibility criteria; both these observations suggest that community-based HTC successfully linked people to care. Finally, offering community-based HTC approaches in addition to facility-based approaches increased HTC coverage seven-fold at the population level.
What Do These Findings Mean?
These findings show that community-based HTC can achieve high HTC uptake rates and can reach HIV-positive individuals earlier, when they still have high CD4 counts. Importantly, they also suggest that the level of linkage to care of community-based HTC is similar to that of facility-based HTC. Although the lower positivity rate of community-based HTC approaches means that more people need to be tested with these approaches than with facility-based HTC to identify the same number of HIV-positive individuals, this downside of community-based HTC is likely to be offset by the earlier identification of HIV-positive individuals, which should improve life expectancy and reduce HIV transmission at the population level. Although further studies are needed to evaluate community-based HTC in other regions of the world, these findings suggest that offering community-based HTC in HIV programs in addition to facility-based testing should support the increased access to HIV prevention and care that is required for the intensification of HIV/AIDS elimination efforts.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001496.
The World Health Organization provides information on all aspects of HIV/AIDS, including information on counseling and testing (in several languages)
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV testing, and on HIV transmission and testing (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
The World AIDS Day Report 2012 provides up-to-date information about the AIDS epidemic and efforts to halt it
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about getting a diagnosis
doi:10.1371/journal.pmed.1001496
PMCID: PMC3742447  PMID: 23966838
7.  Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention 
PLoS Medicine  2015;12(9):e1001874.
Background
Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality.
Methods and Findings
In the “pre-intervention 2010” (from January 2010 to December 2010) and “pre-intervention 2011” (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the “post-intervention 2012” (from July 2012 to June 2013) and “post-intervention 2013” (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6–18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27–141)/43 d (IQR 15–113) to 5 d (IQR 2–12)/5 d (IQR 2–13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239–0.620] and 0.380 [95% CI 0.233–0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226–0.603] and 0.361 [95% CI 0.221–0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52.
Conclusions
Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.
In a before and after analysis, Zunyou Wu and colleagues assess the impact on mortality of an HIV test and treat intervention in two counties in Guangxi, China.
Editors' Summary
Background
Every year, about 2.1 million people (mostly living in resource-limited countries) are newly infected with HIV, the virus that causes AIDS and that has killed 39 million people over the past three decades. HIV, which is usually transmitted through unprotected sex with an infected individual, gradually destroys CD4 lymphocytes and other immune system cells, leaving HIV-positive individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within ten years of infection. Then, in 1996, effective antiretroviral therapy (ART) became available, and, for people living in high-income countries, HIV became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. In 2003, the international community began to work towards achieving universal ART coverage. By 2013, about 12.9 million people living with HIV (a third of all HIV-positive people) had access to ART, and the rate of AIDS-related deaths had fallen by a third from its 2005 peak.
Why Was This Study Done?
Unfortunately, in many countries, late diagnosis of HIV infection, incomplete linkage to care after diagnosis, and high rates of loss to follow-up before and after ART initiation remain major barriers to effective HIV/AIDS treatment and to maximization of the preventative benefits of ART: as well as keeping HIV-positive people healthy, ART also reduces their chances of transmitting HIV to a sexual partner. Here, the researchers investigate whether a simplified “test and treat” intervention can reduce HIV/AIDS mortality (death) rates in China by reducing these barriers. Currently, CD4 testing is offered to people in China only after an initial HIV diagnosis has been confirmed using a second type of test. This standard-of-care policy introduces a delay into ART initiation because a CD4 count below 350 cells/μl blood is the primary determinant of eligibility for treatment through the Chinese national free ART program. By contrast, the simplified test and treat intervention, which is designed to be completed within a week of the patient’s first positive HIV test result, incorporates immediate HIV confirmatory testing, pre-ART CD4 testing, pre-treatment counseling, and ART initiation regardless of CD4 count.
What Did the Researchers Do and Find?
The researchers followed about 1,000 patients who tested positive for HIV at health care facilities in two counties in Guangxi (one of the Chinese provinces most heavily affected by HIV/AIDS) in two 12-month pre-intervention phases, during which patients followed the standard-of-care process, and two 12-month post-intervention phases, during which patients were offered the simplified test and treat intervention. About 65% and 97% of the patients received baseline CD4 testing during the pre-intervention and post-intervention phases, respectively. Following the structural intervention, the time from HIV confirmation to ART initiation decreased from around 50 days to five days, and the proportion of individuals who initiated ART increased from below 36% to above 90% among all the patients and from below 47% to above 93% among patients eligible for treatment under the standard-of-care policy. Notably, the mortality rate decreased from about 26% to about 10% among all the study participants following the intervention, and from about 37% to about 13% among the participants eligible for ART under the standard-of-care policy. Finally, the researchers estimated that the cost of each death prevented by the intervention was about US$234.52 over the study period; importantly, most of this cost was accrued during the initial year of the intervention.
What Do These Findings Mean?
These findings indicate that, in the two Chinese counties involved in this study, the simplified test and treat intervention—which incorporated a streamlined, standardized time frame for HIV diagnosis and expanded access to ART—promoted successful engagement in care among HIV-positive individuals and was associated with a 62% reduction in mortality. Moreover, the intervention required very little further investment once it had been set up and should, therefore, be sustainable. Because the design of the simplified test and treat intervention took into account the characteristics of the HIV epidemic and the health care structure in China, these findings may not be fully generalizable to other countries. In addition, reliance on a pre-intervention/post-intervention study design, rather than a controlled trial, may limit the accuracy of these findings. Nevertheless, these results suggest that the implementation of integrated HIV testing and immediate access to ART regardless of CD4 count has the potential to optimize the individual and public health impacts of ART by ensuring that fewer patients are lost along the multistage continuum of HIV testing and treatment.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001874.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART and on HIV/AIDS in China; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its Consolidated Guidelines on the Use of Antiretroviral Therapy for Treating and Preventing HIV Infection, its recently released consolidated guidelines on HIV testing, and information on the WHO/UNAIDS Treatment 2.0 strategy, an initiative to expand access to HIV testing and ART
The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy
doi:10.1371/journal.pmed.1001874
PMCID: PMC4562716  PMID: 26348214
8.  Long-Term Biological and Behavioural Impact of an Adolescent Sexual Health Intervention in Tanzania: Follow-up Survey of the Community-Based MEMA kwa Vijana Trial 
PLoS Medicine  2010;7(6):e1000287.
David Ross and colleagues conduct a follow-up survey of the community-based MEMA kwa Vijana (“Good things for young people”) trial in rural Tanzania to assess the long-term behavioral and biological impact of an adolescent sexual health intervention.
Background
The ability of specific behaviour-change interventions to reduce HIV infection in young people remains questionable. Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in ten randomly chosen intervention communities in rural Tanzania, within a community randomised trial (see below; NCT00248469). The intervention consisted of teacher-led, peer-assisted in-school education, youth-friendly health services, community activities, and youth condom promotion and distribution. Process evaluation in 1999–2002 showed high intervention quality and coverage. A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 (HSV-2) seroprevalence but found substantial improvements in SRH knowledge, reported attitudes, and some reported sexual behaviours. It was postulated that the impact on “upstream” knowledge, attitude, and reported behaviour outcomes seen at the 3-year follow-up would, in the longer term, lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes. A further impact evaluation survey in 2007/8 (∼9 years post-intervention) tested this hypothesis.
Methods and Findings
This is a cross-sectional survey (June 2007 through July 2008) of 13,814 young people aged 15–30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial (1999–2002). Prevalences of the primary outcomes HIV and HSV-2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio [aPR] 0.91, 95%CI 0.50–1.65; females aPR 1.07, 95%CI 0.68–1.67) or HSV-2 (males aPR 0.94, 95%CI 0.77–1.15; females aPR 0.96, 95%CI 0.87–1.06). The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime (aPR 0.87, 95%CI 0.78–0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR 1.34, 95%CI 1.07–1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies, or other reported sexual behaviours. The study population was likely to have been, on average, at lower risk of HIV and other sexually transmitted infections compared to other rural populations, as only youth who had reached year five of primary school were eligible.
Conclusions
SRH knowledge can be improved and retained long-term, but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated.
Trial Registration
ClinicalTrials.gov NCT00248469
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people become infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. HIV is most often spread through unprotected sex with an infected partner, so individuals can reduce their risk of HIV infection by abstaining from sex, by delaying first sex, by having few partners, and by always using a condom. And, because nearly half of new HIV infections occur among youths (15- to 24-year-olds), programs targeted at adolescents that encourage these protective behaviors could have a substantial impact on the HIV epidemic. One such program is the MEMA kwa Vijana (“Good things for young people”) program in rural Tanzania. This program includes in-school sexual and reproductive health (SRH) education for pupils in their last three years of primary education (12- to 15-year-olds) that provides them with the knowledge and skills needed to delay sexual debut and to reduce sexual risk taking. Between 1999 and 2002, the program was trialed in ten randomly chosen rural communities in the Mwanza Region of Tanzania; ten similar communities that did not receive the intervention acted as controls. Since 2004, the program has been scaled up to cover more communities.
Why Was This Study Done?
Although the quality and coverage of the MEMA kwa Vijana program was good, a 2001/2002 evaluation found no evidence that the intervention had reduced the incidence of HIV (the proportion of the young people in the trial who became HIV positive during the follow-up period) or the prevalence (the proportion of the young people in the trial who were HIV positive at the end of the follow-up period) of herpes simplex virus 2 (HSV-2, another sexually transmitted virus). However, the evaluation found improvements in SRH knowledge, in reported sexual attitudes, and in some reported sexual behaviors. Evaluations of other HIV prevention programs in other developing countries have also failed to provide strong evidence that such programs decrease the risk of HIV infection or other biological outcomes such as the frequency of other sexually transmitted infections or pregnancies, even when SRH knowledge improves. One possibility is that it takes some time for improved SRH knowledge to be reflected in true changes in sexual behavior and in HIV prevalence. In this follow-up study, therefore, researchers investigate the long-term impact of the MEMA kwa Vijana program on HIV and HSV-2 prevalence and ask whether the improvement in knowledge, reported attitudes and sexual risk behaviours seen at the 3-year follow up has persisted.
What Did the Researchers Do and Find?
In 2007/8, the researchers surveyed nearly 14,000 young people who had attended the trial schools between 1999 and 2002. Each participant had their HIV and HSV-2 status determined and answered questions (for example, “can HIV be caught by sexual intercourse (making love) with someone,” and “if a girl accepts a gift from a boy, must she agree to have sexual intercourse (make love) with him?”) to provide three composite sexual knowledge scores and one composite attitude score. 1.8% of the male and 4.0% of the female participants were HIV positive; 25.9% and 41.4% of the male and female participants, respectively, were HSV-2 positive. The prevalences were similar among the young people whose trial communities had been randomly allocated to receive the MEMA kwa Vijana Program and those whose communities had not received it, indicating that the MEMA kwa Vijana intervention program had not reduced the risk of HIV or HSV-2. The intervention program was associated, however, with a reduction in the proportion of men reporting more than four sexual partners in their lifetime and with an increase in reported condom use at last sex with a non-regular partner among women. Finally, although the intervention had still increased SRH knowledge, it now had had no impact on reported attitudes to sexual risk, reported pregnancies, or other reported risky sexual behaviors beyond what might have happened due to chance.
What Do These Findings Mean?
These findings indicate that, in the MEMA kwa Vijana trial, SRH knowledge improved and that this improved knowledge was retained for many years. Disappointingly, however, this intervention program had only a limited effect on reported sexual behaviors and no effect on HIV and HSV-2 prevalence at the 9-year follow-up. Although these findings may not be generalizable to other adolescent populations, they suggest that intervention programs that target only adolescents might not be particularly effective. Young people might find it hard to put their improved skills and knowledge into action when challenged, for example, by widespread community attitudes such as acceptance of older male–younger female relationships. Thus, the researchers suggest that the integration of youth HIV prevention programs within risk reduction programs that tackle sexual norms and expectations in all age groups might be a more successful approach and should be evaluated.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000287.
This study is further discussed in a PLoS Medicine Perspective by Rachel Jewkes
More information about the MEMA kwa Vijana program is available at their Web site
Information is available from the Programme for Research and Capacity Building in Sexual and Reproductive Health and HIV in Developing Countries on recent and ongoing research on HIV infection and other STIs
Information is available from the World Health Organization on HIV and on the health of young people
Information on HIV is available from UNAIDS
Information on HIV in children and adolescents is available from UNICEF
Information on HIV prevention interventions in the education sector is available from UNESCO
Information on HIV infection and AIDS is available from the US National Institute of Allergy and Infectious Diseases
The US Centers for Disease Control and Prevention provide information on HIV/AIDS and on HIV/AIDS among youth (in English and Spanish)
HIV InSitehas comprehensive information on all aspects of HIV/AIDS, including links to information on the prevention of HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS prevention and AIDS and sex education (in English and Spanish)
doi:10.1371/journal.pmed.1000287
PMCID: PMC2882431  PMID: 20543994
9.  Supervised and Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic Review 
PLoS Medicine  2013;10(4):e1001414.
By systematically reviewing the literature, Nitika Pant Pai and colleagues assess the evidence base for HIV self tests both with and without supervision.
Background
Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies.
Methods and Findings
Seven databases (Medline [via PubMed], Biosis, PsycINFO, Cinahl, African Medicus, LILACS, and EMBASE) and conference abstracts of six major HIV/sexually transmitted infections conferences were searched from 1st January 2000–30th October 2012. 1,221 citations were identified and 21 studies included for review. Seven studies evaluated an unsupervised strategy and 14 evaluated a supervised strategy. For both strategies, data on acceptability (range: 74%–96%), preference (range: 61%–91%), and partner self-testing (range: 80%–97%) were high. A high specificity (range: 99.8%–100%) was observed for both strategies, while a lower sensitivity was reported in the unsupervised (range: 92.9%–100%; one study) versus supervised (range: 97.4%–97.9%; three studies) strategy. Regarding feasibility of linkage to counselling and care, 96% (n = 102/106) of individuals testing positive for HIV stated they would seek post-test counselling (unsupervised strategy, one study). No extreme adverse events were noted. The majority of data (n = 11,019/12,402 individuals, 89%) were from high-income settings and 71% (n = 15/21) of studies were cross-sectional in design, thus limiting our analysis.
Conclusions
Both supervised and unsupervised testing strategies were highly acceptable, preferred, and more likely to result in partner self-testing. However, no studies evaluated post-test linkage with counselling and treatment outcomes and reporting quality was poor. Thus, controlled trials of high quality from diverse settings are warranted to confirm and extend these findings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (most living in resource-limited countries) are currently infected with HIV, the virus that causes AIDS, and about 2.5 million people become infected with HIV every year. HIV is usually transmitted through unprotected sex with an infected partner. HIV infection is usually diagnosed by looking for antibodies to HIV in blood or saliva. Early during infection, the immune system responds to HIV by beginning to make antibodies that recognize the virus and target it for destruction. “Seroconversion”—the presence of detectable amounts of antibody in the blood or saliva—usually takes 6–12 weeks. Rapid antibody-based tests, which do not require laboratory facilities, can provide a preliminary result about an individual's HIV status from a simple oral swab or finger stick sample within 20 minutes. However preliminary rapid positive results have to be confirmed in a laboratory, which may take a few days or weeks. If positive, HIV infection can be controlled but not cured by taking a daily cocktail of powerful antiretroviral drugs throughout life.
Why Was This Study Done?
To reduce the spread of HIV, it is essential that HIV-positive individuals get tested, change behaviors avoid transmitting the virus to other people by, for example, always using a condom during sex, and if positive get on to treatment that is available worldwide. Treatment also reduces transmission of virus to the partner and controls the virus in the community. However, only half the people currently living with HIV know their HIV status, a state of affairs that increases the possibility of further HIV transmission to their partners and children. HIV positive individuals are diagnosed late with advanced HIV infection that costs health care services. Although health care facility-based HIV testing has been available for decades, people worry about stigma, visibility, and social discrimination. They also dislike the lack of privacy and do not like having to wait for their test results. Self-testing (i.e., self-test conduct and interpretation) might alleviate some of these barriers to testing by allowing individuals to determine their HIV status in the privacy of their home and could, therefore, increase the number of individuals aware of their HIV status. This could possibly reduce transmission and, through seeking linkages to care, bring HIV under control in communities. In some communities and countries, stigma of HIV prevents people from taking action about their HIV status. Indeed, an oral (saliva-based) HIV self-test kit is now available in the US. But how acceptable, feasible, and accurate is self-testing by lay people, and will people who find themselves self-test positive seek counseling and treatment? In this systematic review (a study that uses pre-defined criteria to identify all the research on a given topic), the researchers examine these issues by analyzing data from studies that have evaluated supervised self-testing (self-testing and counseling aided by a health-care professional) and unsupervised self-testing (self-testing performed without any help but with counseling available by phone or internet).
What Did the Researchers Do and Find?
The researchers identified 21 eligible studies, two-thirds of which evaluated oral self-testing and a third of which evaluated blood-based self-testing. Seven studies evaluated an unsupervised self-testing strategy and 14 evaluated a supervised strategy. Most of the data (89%) came from studies undertaken in high-income settings. The study populations varied from those at high risk of HIV infection to low-risk general populations. Across the studies, acceptability (defined as the number of people who actually self-tested divided by the number who consented to self-test) ranged from 74% to 96%. With both strategies, the specificity of self-testing (the chance of an HIV-negative person receiving a negative test result is true negative) was high but the sensitivity of self-testing (the chance of an HIV-positive person receiving a positive test result is indeed a true positive) was higher for supervised than for unsupervised testing. The researchers also found evidence that people preferred self-testing to facility-based testing and oral self-testing to blood-based self testing and, in one study, 96% of participants who self-tested positive sought post-testing counseling.
What Do These Findings Mean?
These findings provide new but limited information about the feasibility, acceptability, and accuracy of HIV self-testing. They suggest that it is feasible to implement both supervised and unsupervised self-testing, that both strategies are preferred to facility-based testing, but that the accuracy of self-testing is variable. However, most of the evidence considered by the researchers came from high-income countries and from observational studies of varying quality, and data on whether people self-testing positive sought post-testing counseling (linkage to care) were only available from one evaluation of unsupervised self-testing in the US. Consequently, although these findings suggest that self-testing could engage individuals in finding our their HIV status and thereby help modify behavior thus, reduce HIV transmission in the community, by increasing the proportion of people living with HIV who know their HIV status. The researchers suggested that more data from diverse settings and preferably from controlled randomized trials must be collected before any initiatives for global scale-up of self-testing for HIV infection are implemented.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001414.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV testing, and on HIV transmission and testing (in English and Spanish)
The UK National Health Service Choices website provides information about all aspects of HIV and AIDS; a “behind the headlines” article provides details about the 2012 US approval for an over-the-counter HIV home-use test
The 2012 World AIDS Day Report provides information about the percentage of people living with HIV who are aware of their HIV status in various African countries, as well as up-to-date information about the AIDS epidemic
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about getting a diagnosis
doi:10.1371/journal.pmed.1001414
PMCID: PMC3614510  PMID: 23565066
10.  HIV, Gender, Race, Sexual Orientation, and Sex Work: A Qualitative Study of Intersectional Stigma Experienced by HIV-Positive Women in Ontario, Canada 
PLoS Medicine  2011;8(11):e1001124.
Mona Loutfy and colleagues used focus groups to examine experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada.
Background
HIV infection rates are increasing among marginalized women in Ontario, Canada. HIV-related stigma, a principal factor contributing to the global HIV epidemic, interacts with structural inequities such as racism, sexism, and homophobia. The study objective was to explore experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada.
Methods and Findings
We conducted a community-based qualitative investigation using focus groups to understand experiences of stigma and discrimination and coping methods among HIV-positive women from marginalized communities. We conducted 15 focus groups with HIV-positive women in five cities across Ontario, Canada. Data were analyzed using thematic analysis to enhance understanding of the lived experiences of diverse HIV-positive women. Focus group participants (n = 104; mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender) described stigma/discrimination and coping across micro (intra/interpersonal), meso (social/community), and macro (organizational/political) realms. Participants across focus groups attributed experiences of stigma and discrimination to: HIV-related stigma, sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work. Coping strategies included resilience (micro), social networks and support groups (meso), and challenging stigma (macro).
Conclusions
HIV-positive women described interdependent and mutually constitutive relationships between marginalized social identities and inequities such as HIV-related stigma, sexism, racism, and homo/transphobia. These overlapping, multilevel forms of stigma and discrimination are representative of an intersectional model of stigma and discrimination. The present findings also suggest that micro, meso, and macro level factors simultaneously present barriers to health and well being—as well as opportunities for coping—in HIV-positive women's lives. Understanding the deleterious effects of stigma and discrimination on HIV risk, mental health, and access to care among HIV-positive women can inform health care provision, stigma reduction interventions, and public health policy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
HIV-related stigma and discrimination—prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV—is a major factor contributing to the global HIV epidemic. HIV-related stigma, which devalues and stereotypes people living with HIV, increases vulnerability to HIV infection by reducing access to HIV prevention, testing, treatment, and support. At the personal (micro) level, HIV-related stigma can make it hard for people to take tests to determine their HIV status or to tell other people that they are HIV positive. At the social/community (meso) level, it can mean that HIV-positive people are ostracized from their communities. At the organizational/political (macro) level, it can mean that health-care workers treat HIV-positive people differently and that governments are deterred from taking fast, effective action against the HIV epidemic. In addition, HIV-related stigma is negatively associated with well-being among people living with HIV. Thus, among HIV-positive people, those who have experienced HIV-related stigma have higher levels of mental and physical illness.
Why Was This Study Done?
Racism (oppression and inequity founded on ethno-racial differences), sexism and gender discrimination (oppression and inequity based on gender bias in attitudes), and homophobia and transphobia (discrimination, fear, hostility, and violence towards nonheterosexual and transgender people, respectively) can also affect access to HIV services. However, little is known about how these different forms of stigma and discrimination interact (intersect). A better understanding of the effect of intersecting stigmas on people living with HIV could help in the development of stigma reduction interventions and HIV prevention, treatment and care programs, and could help to control global HIV infection rates. In this qualitative study (an analysis of people's attitudes and experiences rather than numerical data), the researchers investigate the intersection of HIV-related stigma, racism, sexism and gender discrimination, homophobia and transphobia among marginalized HIV-positive women in Ontario, Canada. As elsewhere in the world, HIV infection rates are increasing among women in Canada. Nearly 25% of people living with HIV in Canada are women and about a quarter of all new infections are in women. Moreover, there is a disproportionately high infection rate among marginalized women in Canada such as sex workers and lesbian, bisexual, and queer women.
What Did the Researchers Do and Find?
The researchers held 15 focus groups with 104 marginalized HIV-positive women who were recruited by word-of-mouth and through flyers circulated in community agencies serving women of diverse ethno-cultural origins. Each focus group explored topics that included challenges in daily life, medical issues and needs, and issues that were silenced within the participants' communities. The researchers analyzed the data from these focus groups using thematic analysis, an approach that identifies, analyzes, and reports themes in qualitative data. They found that women living with HIV in Ontario experienced multiple types of stigma at different levels. So, for example, women experienced HIV-related stigma at the micro (“If you're HIV-positive, you feel shameful”), meso (“The thing I hate most for people that test positive for HIV is that society ostracizes them”), and macro (“A lot of women are not getting employed because they have to disclose their status”) levels. The women also attributed their experiences of stigma and discrimination to sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work at all three levels and described coping strategies at the micro (resilience; “I always live with hope”), meso (participation in social networks), and macro (challenging stigma) levels.
What Do These Findings Mean?
These findings indicate that marginalized HIV-positive women living in Ontario experience overlapping forms of stigma and discrimination and that these forms of stigma operate over micro, meso, and macro levels, as do the coping strategies adopted by the women. Together, these results support an intersectional model of stigma and discrimination that should help to inform discussions about the complexity of stigma and coping strategies. However, because only a small sample of nonrandomly selected women was involved in this study, these findings need to be confirmed in other groups of HIV-positive women. If confirmed, the complex system of interplay of different forms of stigma revealed here should help to inform health-care provision, stigma reduction interventions, and public-health policy, and could, ultimately, help to bring the global HIV epidemic under control.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001124.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment; its publication HIV and stigma deals with HIV-related stigma in the UK
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on women, HIV, and AIDS, on HIV and AIDS stigma and discrimination, and on HIV/AIDS statistics for Canada (in English and Spanish)
The People Living with Stigma Index to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma; its website will soon include a selection of individual stories about HIV-related stigma
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001124
PMCID: PMC3222645  PMID: 22131907
11.  Stakeholders’ perceptions on factors influencing male involvement in prevention of mother to child transmission of HIV services in Blantyre, Malawi 
BMC Public Health  2014;14:691.
Background
Male Involvement (MI) in the Prevention of Mother to Child Transmission (PMTCT) of Human Immunodeficiency Virus (HIV) services is essential in a patriarchal society where men are decision makers of the household. Male partners have a role in the woman’s risk of acquiring HIV, uptake of HIV testing and participation in Mother to Child Transmission (MTCT) prevention programmes. Although MI is important for uptake of PMTCT interventions, it remains low in Africa. The purpose of this study was to identify factors that promote and hinder MI in PMTCT services in antenatal care (ANC) services in Blantyre, Malawi. Understanding of the factors that influence MI will assist in developing strategies that will involve men more in the programme thereby improving the uptake of PMTCT and HIV testing and counselling services by women and men respectively.
Methods
An exploratory qualitative study was conducted from December 2012 to January 2013 at South Lunzu Health Centre (SLHC) in Blantyre, Malawi. It consisted of six face to face Key Informant Interviews (KIIs) with health care workers and four Focus Group discussions (FGDs) with 18 men and 17 pregnant women attending antenatal care at the clinic. The FGDs were divided according to sex and age. All FGDs and KIIs were digitally recorded and simultaneously transcribed and translated verbatim into English. Data were analysed using thematic content analysis.
Results
Participants in both FGDs and KIIs identified the following barriers: lack of knowledge of MI in PMTCT, socioeconomic factors, relationship issues, timidity to be seen in a woman’s domain, unplanned and or extramarital pregnancies, fear of knowing one's HIV status, unwillingness to be associated with the service, health facility based factors, peer influence and cultural factors. The factors that would potentially promote male involvement were categorized into community, health facility and personal or family level factors.
Conclusions
The factors that may hinder or promote MI arise from different sources. The success of MI lies on recognizing sources of barriers and averting them. Factors that promote MI need to be implemented at different levels of health care.
doi:10.1186/1471-2458-14-691
PMCID: PMC4226974  PMID: 24998152
12.  Changes in HIV Incidence among People Who Inject Drugs in Taiwan following Introduction of a Harm Reduction Program: A Study of Two Cohorts 
PLoS Medicine  2014;11(4):e1001625.
Kenrad Nelson and colleagues report on the association between HIV incidence and exposure to a national harm-reduction program among people who inject drugs in Taiwan.
Please see later in the article for the Editors' Summary
Background
Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.
Methods and Findings
The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6–12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06–0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.
Conclusions
Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and about 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. It is estimated that 5%–10% of all people living with HIV are PWID. Indeed, in some regions of the world the primary route of HIV transmission is through shared drug injection equipment and the prevalence (the proportion of a population that has a specific disease) of HIV infection among PWID is very high. In Asia, for example, more than a quarter of PWID are HIV positive. Because the high prevalence of HIV among PWID poses a global health challenge, bodies such as the Joint United Nations Programme on HIV/AIDS endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include the provision of clean needles and syringes, opioid substitution therapy such as methadone maintenance treatment, and antiretroviral treatment for HIV-positive PWID.
Why Was This Study Done?
Although harm reduction strategies for combating HIV epidemics among PWID have been implemented in several countries, few large-scale studies have examined the association between HIV incidence (the proportion of new cases of HIV in a population per year) and exposure to harm reduction programs among PWID. In this cohort study (an investigation that determines the characteristics of a group of people and then follows them over time), the researchers determine the association between harm reduction programs and HIV incidence among PWID in Taiwan. HIV infections used to be rare among the 60,000 PWID living in Taiwan, but after the introduction of a new HIV strain into the country in 2003, an HIV epidemic spread rapidly. In response, the Taiwanese government introduced a pilot program of harm reduction that included the provision of clean needles and syringes and health education in July 2005. The program was expanded to include methadone maintenance treatment in early 2006 and implemented nationwide in June 2006.
What Did the Researchers Do and Find?
The researchers enrolled two study populations. The first cohort comprised 3,851 PWID who were incarcerated for illicit drug use between 2004 and 2010 and who tested positive for HIV upon admission into prison. By using the BED assay, which indicates whether an HIV infection is recent, the researchers were able to determine the HIV incidence among the prisoners. In 2004, the estimated HIV incidence among prisoners with a history of drug injection was 6.44%. The incidence peaked in 2005 at 18.2%, but fell to 0.3% in 2010.
The second study population comprised 2,473 individuals who were HIV negative on January 1, 2006, and who had been incarcerated for drug use crimes but were released on July 16, 2007, during an amnesty. The researchers regularly interviewed these participants between their release and 2010 about their use of harm reduction interventions, and obtained other data about them (for example, diagnosis of HIV infection) from official databases. Analysis of all these data indicated that, in this cohort, attendance at methadone maintenance treatment clinics and frequent use of needle and syringe services were both associated with a significantly lower HIV incidence.
What Do These Findings Mean?
These findings suggest that the introduction of a comprehensive harm reduction program in Taiwan was associated with a significant reduction in the HIV incidence rate among PWID. These findings must be interpreted with caution, however. First, because the participants in the study were selected from PWID with histories of incarceration, the findings may not be representative of all PWID in Taiwan or of PWID in other countries. Second, PWID who chose to use needle and syringe services or methadone maintenance treatment clinics might have shared other unknown characteristics that affected their risk of HIV infection. Finally, some of the reduction in HIV incidence seen during the study is likely to be associated with the availability of free treatment, which has been offered to all HIV-positive individuals in Taiwan since 1997. Despite these limitations, these findings suggest that countries with a high prevalence and incidence of HIV among PWID should provide comprehensive harm reduction services to their populations to reduce risky drug injection behaviors.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001625.
Information is available from the US National Institute of Allergy and Infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on injecting drug users and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001625
PMCID: PMC3979649  PMID: 24714449
13.  Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study 
PLoS Medicine  2015;12(8):e1001863.
Background
Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART.
Methods and Findings
We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting.
Conclusions
Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care.
In a qualitative study, Katerina Christopoulos examines the reasons for lack of ART usage in patients retained in HIV care.
Editors' Summary
Background
AIDS has killed about 39 million people since the first recorded case of the disease in 1981, and about 35 million people are currently infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an infected partner, destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other serious infections and to unusual cancers. Early in the epidemic, most HIV-positive individuals died from an AIDS-defining illness such as recurrent pneumonia, severe fungal infection, or Kaposi’s sarcoma (a type of cancer). Nowadays, although there is still no cure for AIDS, treatment with antiretroviral drugs (antiretroviral therapy or ART) can hold HIV in check, and, at least in affluent countries, HIV-positive individuals who are on ART now have a near-normal life expectancy.
Why Was This Study Done?
HIV-positive individuals originally only started ART when their CD4 cell count fell below 200 cells/mm3 blood. As ART became more tolerable and more efficacious and as the harmful effects of viremia (HIV in the blood) became clear, the treatment threshold shifted upwards. Nowadays, the US ART guidelines, for example, recommend treatment for all HIV-infected individuals irrespective of cell count and, because ART reduces the risk of an HIV-infected individual transmitting the virus to an uninfected sexual partner, also endorse offering ART for the prevention of HIV transmission. However, 40,000 HIV-positive individuals in the US receive regular HIV care such as virus monitoring but are not prescribed ART, and 5% of individuals starting ART discontinue treatment. It is important to understand why HIV-positive individuals do not use ART, but decision making in relation to ART is complex, involving both the HIV-positive individual and their HIV care provider. HIV-positive individuals may refuse ART if they think their care provider does not believe they really need treatment, for example, and providers may not offer ART to someone they think will not adhere to treatment. Here, the researchers undertake a qualitative patient-provider dyadic study (an analysis of contrasts and overlaps between pairs of narratives) to investigate why some HIV-positive individuals are retained in HIV care but are not on ART and what motivates these individuals to attend HIV care clinics.
What Did the Researchers Do and Find?
The researchers interviewed 20 HIV-positive patients (mainly men) attending two urban US HIV clinics who were either ART-naive or ART-experienced but off ART and their HIV care providers; 15 patient-provider dyads were re-interviewed after at least 3 months and another clinic visit. Patients were asked about their attitudes to ART, their ART usage, and their relationship with their provider. Providers were asked about their ART philosophy, how they discussed ART with their patients, and about their relationship with their paired patient. Nearly all the patients were willing to consider ART and 40% began ART during the study. Reasons given by patients for accepting ART included education about newer, more tolerable drugs but the strength of the provider recommendation of ART was particularly important in patient decisions to accept ART. Specifically, many patients had internalized messages from their providers that their health was too good to warrant ART. Providers for their part often muted the offer of ART to patients experiencing psychosocial problems who they believed would find it hard to adhere to treatment. Finally, patient interviews suggested that motivations for retention in HIV care in the absence of ART included access to viral monitoring and the patient-provider relationship.
What Do These Findings Mean?
These findings may not apply to settings such as HIV clinics in sub-Saharan Africa where patients do not always see the same care provider or to women. Nevertheless, this study identifies the patient-provider encounter as a key factor in ART usage by HIV-positive individuals and highlights the importance of the discussion about ART between patient and provider in the patient’s decision to accept an offer of ART. Given these findings, the researchers make several recommendations about the role of the provider in ART initiation. For example, they suggest that provider assessment of how patients perceive their health status and the implications of ART initiation should be formalized as part of ART counseling. Attention to this and other aspects of the patient-provider encounter, they suggest, may help to improve ART usage among HIV-positive individuals and thereby increase both the individual and public-health benefits of ART.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001863.
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS, including the treatment of HIV/AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care and on treatment as prevention; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection
The 2014 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
doi:10.1371/journal.pmed.1001863
PMCID: PMC4532493  PMID: 26263532
14.  Association of the ANRS-12126 Male Circumcision Project with HIV Levels among Men in a South African Township: Evaluation of Effectiveness using Cross-sectional Surveys 
PLoS Medicine  2013;10(9):e1001509.
Betran Auvert and colleagues report findings from the Bophelo Pele project, a community-based HIV prevention intervention offering free voluntary medical male circumcision (VMMC), that demonstrate an association between VMMC roll-out and a reduction in the incidence and prevalence of HIV in the community.
Please see later in the article for the Editors' Summary
Background
Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African populations; however, little is known about the population-level effect of adult male circumcision (MC) as an HIV prevention method. We assessed the effectiveness of VMMC roll-out on the levels of HIV in the South African township of Orange Farm where the first randomized controlled trial (RCT) to test the effect of VMMC on HIV acquisition was conducted in 2002–2005.
Methods and Findings
The Bophelo Pele project is a community-based campaign against HIV, which includes the roll-out of free VMMC. A baseline cross-sectional biomedical survey was conducted in 2007–2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate 80.7%). In 2010–2011, we conducted a follow-up random survey among 3,338 men aged 15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were interviewed, blood samples were collected and tested for HIV and recent HIV infection (using the BED HIV incidence assay), and MC status was assessed through a clinical examination. Data were analyzed using multivariate and propensity statistical methods.
Owing to the VMMCs performed in the context of the RCT and the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12 (95% CI 0.10–0.14) to 0.53 (95% CI 0.51–0.55). Without these VMMCs, the HIV prevalence rate in 2010–2011 would have been 19% (95% CI 12%–26%) higher (0.147 instead of 0.123).
When comparing circumcised and uncircumcised men, no association of MC status with sexual behavior was detected. Among circumcised and uncircumcised men, the proportion consistently using condoms with non-spousal partners in the past 12 months was 44.0% (95% CI 41.7%–46.5%) versus 45.4% (95% CI 42.2%–48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85–1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI 47.9%–52.9%) versus 44.2% (95% CI 41.3%–46.9%) with wPRR = 1.03 (95% CI 0.95–1.10).
We found a reduction of BED-estimated HIV incidence rate ranging from 57% (95% CI 29%–76%) to 61% (95% CI 14%–83%) among circumcised men in comparison with uncircumcised men.
Conclusions
Findings suggest that the roll-out of VMMC in Orange Farm is associated with a significant reduction of HIV levels in the community. The main limitation of the study is that it was not randomized and cannot prove a causal association. The roll-out of VMMC among adults in sub-Saharan Africa should be an international priority and needs to be accelerated to effectively combat the spread of HIV.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year about 2.2 million people (mostly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few sexual partners, and by always using a male or female condom. The results of three randomized controlled trials conducted in sub-Saharan Africa also suggest that voluntary medical male circumcision (VMMC)—the removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce the heterosexual acquisition of HIV in men by 50%–60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision and prioritized 14 east and southern African countries for VMMC roll-out.
Why Was This Study Done?
To date, about 3 million VMMCs have been performed for HIV prevention but it is not known whether “real world” VMMC roll-out programs will replicate the promising results obtained in the earlier trials. Indeed, there are fears that “risk compensation” (an increase in risky sexual behaviors after VMMC) might lead to increased HIV transmission in regions where VMMC is rolled out. In this study, the researchers use sequential cross-sectional surveys (studies that collect data from a group of people at a single time point) to investigate HIV infection levels in men in Orange Farm, a township in South Africa where one of the randomized controlled trials of VMMC was undertaken. The surveys were conducted before and after implementation of the Bophelo Pele project, a community-based campaign against HIV that was initiated in 2008 and that includes free VMMC.
What Did the Researchers Do and Find?
The researchers asked a random sample of nearly 2,000 men aged 15–49 years about their sexual behavior (for example, how many non-spousal partners they had had over the past year), and their intention to become circumcised if uncircumcised in a baseline survey in 2007–2008. The study participants were also offered HIV counseling and testing (including a test that indicated whether the participant had recently become HIV positive) and were examined to see whether they were already circumcised. A similar follow-up survey was conducted in 2010–2011 in which more than 3,000 men were invited to take part. At baseline, 12% of the men surveyed had been circumcised (a prevalence of circumcision of 12%) whereas in the follow-up survey, the overall prevalence of circumcision and the prevalence of circumcision among 15–29 year-olds (an important target group for VMMC roll-out) were 53% and 58%, respectively. The overall HIV prevalence at follow-up was 12% and the researchers estimated that without the VMMCs performed during the Bophelo Pele project and the preceding randomized control trial the prevalence of HIV among men living in Orange Farm would have been 15% in 2011. Using various cut-off values and corrections for a laboratory-based test to measure recent HIV infections, the researchers reported a reduction in the rate of new HIV infections (incidence rate) ranging from 57% to 61% among circumcised men in comparison with uncircumcised men. Importantly, there was no evidence of an association between circumcision status and risky sexual behavior but circumcision was associated with a reduction in the number of men who had recently become HIV positive.
What Do These Findings Mean?
These findings suggest that VMMC roll out in Orange Farm is associated with a reduction in HIV infection levels in the community and that circumcision is not associated with changes in sexual behavior that might affect HIV infection rates. They also suggest that VMMC roll-out is associated with a rapid uptake of VMMC, especially among young men, in an African community where male circumcision is not a social norm. Because this study is not a randomized controlled trial, it cannot establish cause and effect. Thus, although the observed reduction in HIV prevalence among circumcised men compared to uncircumcised men suggests that circumcision provided protection against HIV acquisition within the study population, the results do not conclusively prove this. The findings of this study nevertheless support the continuation and acceleration of the roll-out of adult VMMC in Africa although further studies are needed to show whether VMMC roll-out is also associated with a reduction in HIV acquisition among women and among uncircumcised men.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001509.
Information and resources on male circumcision for HIV prevention are available
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from WHO and UNAIDS on all aspects of HIV/AIDS; the Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS and other international bodies, provides information and tools for VMMC policy development and program implementation; a report entitled Progress in scaling up voluntary medical male circumcision for HIV prevention in East and Southern Africa, January-December 2011 is available
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, on HIV prevention, and on circumcision and HIV (in English and Spanish)
A 2010 PLOS Medicine Research Article by Pascale Lissouba et al. provides more information about the Bophelo Pele project
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline; a personal story about circumcision in Zimbabwe is available
doi:10.1371/journal.pmed.1001509
PMCID: PMC3760784  PMID: 24019763
15.  Routine HIV Testing in Botswana: A Population-Based Study on Attitudes, Practices, and Human Rights Concerns 
PLoS Medicine  2006;3(7):e261.
Background
The Botswana government recently implemented a policy of routine or “opt-out” HIV testing in response to the high prevalence of HIV infection, estimated at 37% of adults.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana to assess knowledge of and attitudes toward routine testing, correlates of HIV testing, and barriers and facilitators to testing, 11 months after the introduction of this policy. Most participants (81%) reported being extremely or very much in favor of routine testing. The majority believed that this policy would decrease barriers to testing (89%), HIV-related stigma (60%), and violence toward women (55%), and would increase access to antiretroviral treatment (93%). At the same time, 43% of participants believed that routine testing would lead people to avoid going to the doctor for fear of testing, and 14% believed that this policy could increase gender-based violence related to testing. The prevalence of self-reported HIV testing was 48%. Adjusted correlates of testing included female gender (AOR = 1.5, 95% CI = 1.1–1.9), higher education (AOR = 2.0, 95% CI = 1.5–2.7), more frequent healthcare visits (AOR = 1.9, 95% CI = 1.3–2.7), perceived access to HIV testing (AOR = 1.6, 95% CI = 1.1–2.5), and inconsistent condom use (AOR = 1.6, 95% CI = 1.2–2.1). Individuals with stigmatizing attitudes toward people living with HIV and AIDS were less likely to have been tested for HIV/AIDS (AOR = 0.7, 95% CI = 0.5–0.9) or to have heard of routine testing (AOR = 0.59, 95% CI = 0.45–0.76). While experiences with voluntary and routine testing overall were positive, 68% felt that they could not refuse the HIV test. Key barriers to testing included fear of learning one's status (49%), lack of perceived HIV risk (43%), and fear of having to change sexual practices with a positive HIV test (33%).
Conclusions
Routine testing appears to be widely supported and may reduce barriers to testing in Botswana. As routine testing is adopted elsewhere, measures should be implemented to assure true informed consent and human rights safeguards, including protection from HIV-related discrimination and protection of women against partner violence related to testing.
Editors' Summary
Background.
In 2005, there were 5 million new infections with the human immunodeficiency virus (HIV), and the disease it causes—acquired immunodeficiency syndrome (AIDS)—killed three million people. Despite the increased availability of drugs that can fight HIV (antiretrovirals), the AIDS epidemic continues to grow, particularly in sub-Saharan Africa. To halt it, more needs to be done to prevent the spread of HIV. Education about safe sex can help—HIV is most commonly spread through unprotected sex with an infected partner—but increasing HIV testing is of paramount importance. Unfortunately, the uptake of voluntary counseling and testing in sub-Saharan Africa is worryingly low. Fear of being stigmatized—socially disgraced—and discriminated against, fears about the positive result itself, and worries about access to antiretroviral drugs are all putting people off being tested.
Why Was This Study Done?
In Botswana, one in three adults is infected with HIV. Since 2002, antiretroviral drugs have been freely available but enrollment in the Botswana National Treatment Program during its first two years was slow, in part due to inadequate uptake of voluntary HIV testing. Consequently, in early 2004, the government introduced a policy of routine HIV testing in which all patients are tested for HIV when they visit their doctor unless they opt out. A major aim of this approach to HIV testing, which was formally recommended in June 2004 by UNAIDS and the World Health Organization, is to increase uptake of HIV testing and treatment, and to reduce HIV-related stigma by treating the HIV test like any other routine medical procedure. However, there are fears that the policy could back-fire—people might not visit their doctors, for example, because they are afraid of being tested and think that they will not be able to refuse the test. In this study, the researchers investigated knowledge of and attitudes to routine testing in Botswana to understand better the consequences of a routine testing policy.
What Did the Researchers Do and Find?
The researchers interviewed adults throughout Botswana about their knowledge of and attitudes to routine HIV testing 11 months after introduction of the policy. Only half of the participants had heard of routine testing before being interviewed but nearly all were in favor of routine testing. More than half thought it would reduce HIV-related stigma and the violence toward women that is associated with an HIV-positive status. However, almost half believed that routine testing might prevent people from going to the doctor because of fear of testing and a few thought the policy would increase violence against women. Nearly half of the interviewees had had an HIV test and the researchers found, for example, that women were more likely to have been tested than men and that people with stigmatizing attitudes toward people living with HIV and AIDS were less likely to be tested. Fear of learning one's HIV status, lack of perceived risk, and fear of having to change sexual practices if positive all stopped people taking the test. Finally, although experiences with testing were generally positive, approximately two-thirds of interviewees who had been tested felt that it would have been difficult to refuse the test.
What Do These Findings Mean?
These results show that there is widespread support for routine HIV testing in Botswana, a finding supported by recent increases in treatment uptake. Routine testing, write the researchers, holds significant promise for the prevention and treatment of HIV/AIDS in Botswana and elsewhere. In particular, increasing the number of people tested for HIV may reduce HIV-related stigma, which should further increase testing and hopefully slow the spread of HIV. But the results of this study also highlight some areas of concern. Whenever HIV testing policies are implemented, human rights must be protected by ensuring that patients have all the information necessary to make an informed and free decision about being tested, by providing protection for women against violence related to HIV status, and by ensuring total confidentiality. Careful monitoring of Botswana's program and similar programs will be needed to ensure that these human rights are fully met, conclude the researchers.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030261
• US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
• US Department of Health and Human Services information on AIDS
• US Centers for Disease Control and Prevention information on HIV/AIDS
• UNAIDS and World Health Organization 2004 policy statement on HIV testing
• AVERT, a UK-based charity, provides information about HIV and AIDS in Botswana
A cross-sectional, population-based study of 1,268 adults from five districts in Botswana showed that routine HIV testing appears to be widely supported and may reduce barriers to HIV testing.
doi:10.1371/journal.pmed.0030261
PMCID: PMC1502152  PMID: 16834458
16.  The Impact of Company-Level ART Provision to a Mining Workforce in South Africa: A Cost–Benefit Analysis 
PLoS Medicine  2015;12(9):e1001869.
Background
HIV impacts heavily on the operating costs of companies in sub-Saharan Africa, with many companies now providing antiretroviral therapy (ART) programmes in the workplace. A full cost–benefit analysis of workplace ART provision has not been conducted using primary data. We developed a dynamic health-state transition model to estimate the economic impact of HIV and the cost–benefit of ART provision in a mining company in South Africa between 2003 and 2022.
Methods and Findings
A dynamic health-state transition model, called the Workplace Impact Model (WIM), was parameterised with workplace data on workforce size, composition, turnover, HIV incidence, and CD4 cell count development. Bottom-up cost analyses from the employer perspective supplied data on inpatient and outpatient resource utilisation and the costs of absenteeism and replacement of sick workers. The model was fitted to workforce HIV prevalence and separation data while incorporating parameter uncertainty; univariate sensitivity analyses were used to assess the robustness of the model findings. As ART coverage increases from 10% to 97% of eligible employees, increases in survival and retention of HIV-positive employees and associated reductions in absenteeism and benefit payments lead to cost savings compared to a scenario of no treatment provision, with the annual cost of HIV to the company decreasing by 5% (90% credibility interval [CrI] 2%–8%) and the mean cost per HIV-positive employee decreasing by 14% (90% CrI 7%–19%) by 2022. This translates into an average saving of US$950,215 (90% CrI US$220,879–US$1.6 million) per year; 80% of these cost savings are due to reductions in benefit payments and inpatient care costs. Although findings are sensitive to assumptions regarding incidence and absenteeism, ART is cost-saving under considerable parameter uncertainty and in all tested scenarios, including when prevalence is reduced to 1%—except when no benefits were paid out to employees leaving the workforce and when absenteeism rates were half of what data suggested. Scaling up ART further through a universal test and treat strategy doubles savings; incorporating ART for family members reduces savings but is still marginally cost-saving compared to no treatment. Our analysis was limited to the direct cost of HIV to companies and did not examine the impact of HIV prevention policies on the miners or their families, and a few model inputs were based on limited data, though in sensitivity analysis our results were found to be robust to changes to these inputs along plausible ranges.
Conclusions
Workplace ART provision can be cost-saving for companies in high HIV prevalence settings due to reductions in healthcare costs, absenteeism, and staff turnover. Company-sponsored HIV counselling and voluntary testing with ensuing treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with high HIV prevalence.
Gesine Meyer-Rath and colleagues assess whether workplace ART provision can be cost-saving for mining companies in high HIV prevalence settings.
Editors' Summary
Background
Every year, more than 2 million people become newly infected with HIV, the virus that causes AIDS, usually by having unprotected sex with an infected partner. People in the early stages of HIV infection rarely have any symptoms, but, over time, HIV destroys CD4 lymphocytes and other immune system cells, and, eventually, HIV-positive individuals become susceptible to numerous other infections. Because many of these infections are extremely serious, early in the AIDS epidemic, most HIV-infected individuals died within ten years of infection. Then, in 1996, effective antiretroviral therapy (ART)—cocktails of drugs that stop HIV replicating—became available. For people living in affluent countries, HIV/AIDS became a chronic condition, but because ART was expensive, HIV/AIDS remained fatal in low- and middle-income countries. In 2003, the international community began to work towards achieving universal access to ART. By 2013, nearly 13 million HIV-positive people—more than a third of the global HIV-infected population—had access to ART.
Why Was This Study Done?
HIV disease hits individuals in the prime of their working lives, thereby increasing absenteeism, the turnover of labor, and the operating costs of companies working in countries where HIV infection is common (high HIV prevalence). To reduce the economic impact of HIV/AIDS, some companies provide their workforces in such countries with comprehensive HIV services that include counseling and testing, and ART. For example, mining companies in South Africa (where nearly 20% of the working-age population is HIV-positive) provide HIV services to their workforces. However, although there is strong evidence that HIV disease increases the cost of doing business, a full cost–benefit analysis (the quantification of both the costs and benefits of a business strategy or medical intervention) of ART provision in the workplace based on real-world data has not been undertaken. Here, the researchers use a mathematical model to estimate the economic impact of HIV and the costs and benefits of company-level ART provision by a South African mining company between 2003 and 2022.
What Did the Researchers Do and Find?
The researchers developed a mathematical model to evaluate the past and future impact and costs to the employer of an ART program provided since 2002 by a coal mining company operating at a number of South African colleries. They fed data on the workforce’s characteristics, the annual number of new HIV infections in the workforce, the CD4 cell counts of HIV-positive employees, healthcare resource utilization, and the costs of absenteeism and labor turnover into the model. The model estimated that, as ART coverage increased from 10% to 97% of eligible employees, increases in the survival and retention of HIV-positive employees and reductions in absenteeism and benefit payments would lead to overall cost savings compared to a scenario of no ART provision. Specifically, the annual cost of HIV to the company would decrease by 5% and the average cost per HIV-positive employee would decrease by 14% by 2022. These changes in costs (which mainly accrue from reductions in benefit payments for death and ill-health retirement and in employee healthcare costs) translate into average savings of nearly US$1 million per year. Finally, scaling up ART coverage through a universal test and treat strategy would double savings, whereas providing ART for family members as well as employees would reduce savings but remain marginally cost-saving compared to no ART.
What Do These Findings Mean?
These findings suggest that workplace ART provision can be cost-saving for companies operating in settings with a high HIV prevalence because of reductions in healthcare costs, absenteeism, and staff turnover. That is, the costs to the employer of providing ART can be less than the costs saved by reducing healthcare use, absenteeism, and worker turnover. The accuracy of these findings depends on the quality of the data used to run the model. However, additional analyses indicate that ART provision is likely to be cost-saving unless people receive no benefits on leaving the workforce or the absenteeism rate is considerably lower than the available data suggest. Thus, the researchers propose that company-sponsored counseling and voluntary HIV testing with treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with a high HIV prevalence. Such a strategy should be cost-saving for employers and might also take some pressure off resource-limited public sector ART programs.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001869.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on ART, universal access to ART, and HIV/AIDS in South Africa; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection
The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it; UNAIDS also provides detailed information about HIV/AIDS in South Africa
Wikipedia has a page about cost–benefit analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The HIV Modelling Consortium has a database of models used in analyzing the impact of HIV and ART, including models such as the one used in this analysis
The International AIDS Economics Network has a library of research on the economics of HIV around the world
doi:10.1371/journal.pmed.1001869
PMCID: PMC4556678  PMID: 26327271
17.  The Safety of Adult Male Circumcision in HIV-Infected and Uninfected Men in Rakai, Uganda 
PLoS Medicine  2008;5(6):e116.
Background
The objective of the study was to compare rates of adverse events (AEs) related to male circumcision (MC) in HIV-positive and HIV-negative men in order to provide guidance for MC programs that may provide services to HIV-infected and uninfected men.
Methods and Findings
A total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO] stage I or II and CD4 counts > 350 cells/mm3) were circumcised in two separate but procedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in rural Rakai, Uganda. Participants were followed at 1–2 d and 5–9 d, and at 4–6 wk, to assess surgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing were compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were estimated by multiple logistic regression, adjusting for baseline characteristics and postoperative resumption of sex. At enrollment, HIV-positive men were older, more likely to be married, reported more sexual partners, less condom use, and higher rates of sexually transmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were 3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91, 95% confidence interval [CI] 0.47–1.74). Infections were the most common AEs (2.6/100 in HIV-positive versus 3.0/100 in HIV-negative men). Risks of other complications were similar in the two groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIV-positive men and 95.8% in HIV-negative men (p = 0.007). AEs were more common in men who resumed intercourse before wound healing compared to those who waited (AdjOR 1.56, 95% CI 1.05–2.33).
Conclusions
Overall, the safety of MC was comparable in asymptomatic HIV-positive and HIV-negative men, although healing was somewhat slower among the HIV infected. All men should be strongly counseled to refrain from intercourse until full wound healing is achieved.
Trial registration: http://www.ClinicalTrials.gov; for HIV-negative men, #NCT00047073 and for HIV-positive men, #NCT00047073.
Ron Gray and colleagues report on complications of circumcision in HIV-infected and HIV-uninfected men from two related trials in Uganda, finding increased risk with intercourse before wound healing.
Editors' Summary
Background
Worldwide over 33 million people are thought to be living with HIV, and in the absence of a vaccine, preventing its spread is a major health issue. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimate that 68% of 2.5 million new infections worldwide in 2007 took place in sub-Saharan Africa, where 76% of 2.1 million AIDS-related deaths also took place.
One of the principal means of person-to-person transmission of HIV is through sex without the protection of a condom. In parts of Africa, male circumcision is performed in infancy or childhood for religious or cultural reasons or is a traditional rite of passage that marks the transition from child to man. Three trials, in South Africa, Kenya, and Uganda, each found that circumcised men were around half as likely as uncircumcised men to contract HIV from HIV-positive female partners. After reviewing the results, WHO and UNAIDS issued joint advice that male circumcision should be promoted for preventing HIV infection in heterosexual men. As male circumcision does not provide complete protection against HIV infection, they advised that it should be promoted in addition to existing strategies of promoting condom use, abstinence, and a reduction in the number of sexual partners.
Why Was This Study Done?
Although earlier studies had shown that adult male circumcision, when performed in Africa under optimal conditions, is a safe procedure for HIV-negative men, it was not known whether it would also be a safe procedure for HIV-positive men. WHO guidelines recommend that HIV-positive men who request the procedure or have a medical need and no contraindications for it should be circumcised. Also, exclusion of HIV-positive men from circumcision programs may result in stigmatization of these men, and discourage participation by men who do not wish to be tested for HIV. Therefore, it is important to know whether the procedure is safe for HIV-positive men.
What Did the Researchers Do and Find?
The authors compared results from two separate clinical trials carried out with identical procedures in rural Rakai, Uganda. The first, which compared the effect of circumcision with no circumcision in HIV-negative men, was one of the three trials that persuaded the WHO and UNAIDS to promote male circumcision as an HIV prevention strategy. The second Rakai trial did the same comparison but in men who were HIV positive and without symptoms. In this present study, the authors used data from both trials to compare the likelihood of surgery-related complications following circumcision for HIV-negative and HIV-positive men.
The trials recruited men aged 15–49, who were randomly assigned to be circumcised either on enrollment or two years later and were followed up to monitor complications related to the procedure, such as infections, as well as wound healing and when the participant first had sex after the operation. Condom use was recorded at enrollment and six months after enrollment.
The researchers found that most complications were infrequent, mild, and comparable in both groups, with moderate-to-severe complications occurring in only 3%–4% of men in each group. However, delayed wound healing was more frequent in HIV-positive men. Complications were more likely among men who had sex before healing was complete; such men were more likely to be HIV-positive and/or married. Similarly, moderate or severe complications were more likely where men had symptoms of sexually transmitted disease at enrollment, although these were treated before surgery, and these men were more likely to be HIV-positive. Six months after enrollment, similar proportions of HIV-positive and HIV-negative men used condoms consistently, but HIV-positive men were more likely to report using condoms inconsistently than HIV-negative men. However, consistent use of a condom increased among the HIV-positive men compared to when they enrolled.
What Do these Findings Mean?
Circumcision in HIV-positive men without symptoms of AIDS has a low rate of complications, although healing is slower than in HIV-negative men. Because of the greater risk of complications if sex is resumed before full healing, both men and their women partners should be advised to have no sex for at least six weeks after the operation. A separately reported analysis from one of these studies found that women partners are more likely to become HIV infected by HIV-positive men who resume sex prior to complete wound healing. Therefore, for protection of both men and their female partners, it is essential to refrain from intercourse after circumcision until the wound has completely healed.
Because the study found no increased risk of surgical complications in HIV-positive men who undergo circumcision, it should not be necessary to screen men with no symptoms of HIV in future circumcision programs. This should reduce the complexity of implementing such programs and reduce any stigma resulting from exclusion, making it likely that more men will be willing to be circumcised. The rise in consistent condom use among HIV-positive men suggests that messages of safe sex are reaching an important target group and changing their behavior, and that circumcision does not make men less likely to use a condom.
The authors also noted that the rates of complications they observed were low compared with those following traditional circumcision procedures. Others have found that circumcision carried out under unsafe conditions has a high rate of complications. The authors of this study comment that the resources and standards of surgery during the trial represented best practice and that to attain similarly low rates of complications—and the confidence of men in the safety of the procedure—there is a need to ensure sufficient resources and high standards of training.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050116.
WHO and the UNAIDS issued a joint report recommending male circumcision for HIV prevention and another on the HIV epidemic worldwide in December 2007
An information pack here on male circumcision and HIV prevention has also been developed jointly by WHO/UNAIDS, the United Nations International Children's Emergency Fund (UNICEF), the United Nations Population Fund (UNFPA), and the World Bank
The University of California San Francisco's HIV InSite provides information on HIV prevention, treatment, and policy
AEGIS is the world's largest searchable database on HIV and AIDS
The National AIDS Trust provides information on HIV prevention
doi:10.1371/journal.pmed.0050116
PMCID: PMC2408615  PMID: 18532873
18.  The Role of Viral Introductions in Sustaining Community-Based HIV Epidemics in Rural Uganda: Evidence from Spatial Clustering, Phylogenetics, and Egocentric Transmission Models 
PLoS Medicine  2014;11(3):e1001610.
Using different approaches to investigate HIV transmission patterns, Justin Lessler and colleagues find that extra-community HIV introductions are frequent and likely play a role in sustaining the epidemic in the Rakai community.
Please see later in the article for the Editors' Summary
Background
It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities—home to two-thirds of the African population—is driven by intra-community sexual networks versus viral introductions from outside of communities.
Methods and Findings
We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7–3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%–42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%–70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai.
Conclusions
Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people (25 million of whom live in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS, and about 2.3 million people become newly infected every year. HIV destroys immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled by taking antiretroviral drugs (antiretroviral therapy, or ART) daily throughout life. Although originally available only to people living in wealthy countries, recent political efforts mean that 9.7 million people in low- and middle-income countries now have access to ART. However, ART does not cure HIV infection, so prevention of viral transmission remains extremely important. Because HIV is usually transmitted through unprotected sex with an infected partner, individuals can reduce their risk of infection by abstaining from sex, by having one or a few partners, and by using condoms. Male circumcision also reduces HIV transmission. In addition to reducing illness and death among HIV-positive people, ART also reduces HIV transmission.
Why Was This Study Done?
Effective HIV control requires an understanding of how HIV spreads through sexual networks. These networks include sexual partnerships between individuals in households, between community members in different households, and between individuals from different communities. Local sexual networks (household and intra-community sexual partnerships) are sometimes assumed to be the dominant driving force in HIV spread in sub-Saharan Africa, but are viral introductions from sexual partnerships with individuals outside the community also important? This question needs answering because the effectiveness of interventions such as ART as prevention partly depends on how many new infections in an intervention area are attributable to infection from partners residing in that area and how many are attributable to infection from partners living elsewhere. Here, the researchers use three analytical methods—spatial clustering statistics, viral phylogenetics, and egocentric transmission modeling—to ask whether HIV transmission in rural Uganda is driven predominantly by intra-community sexual networks. Spatial clustering analysis uses the geographical coordinates of households to measure the tendency of HIV-infected people to cluster spatially at scales consistent with community transmission. Viral phylogenetic analysis examines the genetic relatedness of viruses; if transmission is through local networks, viruses in newly infected individuals should more closely resemble viruses in other community members than those in people outside the community. Egocentric transmission modelling uses information on the locations of recent sexual partners to estimate the proportions of new transmissions from household, intra-community, and extra-community partners.
What Did the Researchers Do and Find?
The researchers applied their three analytical methods to data collected from 14,594 individuals living in 46 communities (governmental administrative units) in Rakai District, Uganda. Spatial clustering analysis indicated that individuals who lived in households with individuals with incident HIV (newly diagnosed) or prevalent HIV (previously diagnosed) were 3.2 times more likely than the general population to be HIV-positive themselves. Spatial clustering outside households was relatively weak, however, and was confined to distances of less than half a kilometer. Viral phylogenetic analysis indicated that 44% of phylogenetic clusters (viruses with related genetic sequences found in more than one individual) were within households, but that 40% of clusters crossed community borders. Finally, analysis of the locations of self-reported sexual partners indicated that 39% of new viral transmissions occurred within stable household partnerships, but that among people newly infected by extra-household partners, nearly two-thirds were infected by partners from outside their community.
What Do These Findings Mean?
The results of all three analyses suggest that HIV introductions into communities are frequent and are likely to play an important role in sustaining HIV transmission in the Rakai District. Specifically, within this rural HIV-endemic region (a region where HIV infection is always present), viral introductions combined with intra-household transmission account for the majority of new infections, although community-based sexual networks also play a critical role in HIV transmission. These findings may not be generalizable to the broader Ugandan population or to other regions of Africa, and their accuracy is likely to be limited by the use of self-reported sexual partner data. Nevertheless, these findings indicate that the dynamics of HIV transmission in rural Uganda (and probably elsewhere) are complex. Consequently, to halt the spread of HIV, prevention efforts will need to be implemented at spatial scales broader than individual communities, and key populations that are likely to introduce HIV into communities will need to be targeted.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001610.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda and on HIV prevention strategies (in English and Spanish)
The UNAIDS Report on the Global AIDS Epidemic 2013 provides up-to-date information about the AIDS epidemic and efforts to halt it
The Center for AIDS Prevention Studies (University of California, San Francisco) has a fact sheet about sexual networks and HIV prevention
Wikipedia provides information on spatial clustering analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
A PLOS Computational Biology Topic Page (a review article that is a published copy of record of a dynamic version of the article as found in Wikipedia) about viral phylodynamics is available
Personal stories about living with HIV/AIDS are available through Avert, NAM/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001610
PMCID: PMC3942316  PMID: 24595023
19.  The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study 
PLoS Medicine  2012;9(10):e1001323.
Gabriela Gomez and colleagues developed a mathematical model of the HIV epidemic among men who have sex with men and transwomen in Lima, Peru to explore whether HIV pre-exposure prophylaxis could be a cost-effective addition to existing HIV prevention strategies.
Background
HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.
Methods and Findings
We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.
Conclusions
A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Without a vaccine, the only ways to halt the global HIV epidemic are prevention strategies that reduce transmission of the HIV virus. Up until recently, behavioral strategies such as condom use and reduction of sexual partners have been at the center of HIV prevention. In the past few years, several biological prevention measures have also been shown to be effective in reducing (though not completely preventing) HIV transmission. These include male circumcision, treatment for prevention (giving antiretroviral drugs to HIV-infected people, before they need it for their own health, to reduce their infectiousness) and pre-exposure prophylaxis (or PrEP), in which HIV-negative people use antiretroviral drugs to protect themselves from infection. One PrEP regimen (a daily pill containing two different antiretrovirals) has been shown in a clinical trial to reduce new infections by 44% in of men who have sex with men (MSM). In July 2012, the US Food and Drug Administration approved this PrEP regimen to reduce the risk of HIV infection in uninfected men and women who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. The approval makes it clear that PrEP needs to be used in combination with safe sex practices.
Why Was This Study Done?
Clinical trials have shown that PrEP can reduce HIV infections among participants, but they have not examined the consequences PrEP could have at the population level. Before decision-makers can decide whether to invest in PrEP programs, they need to know about the costs and benefits at the population level. Besides the price of the drug itself, the costs include HIV testing before starting PrEP, as well as regular tests thereafter. The health benefits of reducing new HIV infections are calculated in “disability-adjusted life years” (or DALYs) averted. One DALY is equal to one year of healthy life lost. Other benefits include future savings in lifelong HIV/AIDS treatment for every person whose infection is prevented by PrEP.
This study estimates the potential costs and health benefits of several hypothetical PrEP roll-out scenarios among the community of MSM in Lima, Peru. The scientists chose this community because many of the participants in the clinical trial that showed that PrEP can reduce infections came from this community, and they therefore have some knowledge on how PrEP affects HIV infection rates and behavior in this population. Because the HIV epidemic in Lima is concentrated among MSM, similar to most of Latin America and several other developed countries, the results might also be relevant for the evaluation of PrEP in other places.
What Did the Researchers Do and Find?
For their scenarios, the researchers looked at “high coverage” and “low coverage” scenarios, in which 20% and 5% of uninfected individuals use PrEP, respectively. They also divided the MSM community into those at lower risk of becoming infected and those at higher risk. The latter group consisted of transwomen at higher risk (transsexuals and transvestites with many sexual partners) and male sex workers. In a “uniform coverage” scenario, PrEP is equally distributed among all MSM. “Prioritized scenarios” cover transwomen at higher risk and sex workers preferentially. Two additional important factors for the estimated benefits are treatment adherence (i.e., whether people take the pills they have been prescribed faithfully over long periods of time even though they are not sick) and changes in risk behavior (i.e., whether the perceived protection provided by PrEP leads to more unprotected sex).
The cost estimates for PrEP included the costs of the drug itself and HIV tests prior to PrEP prescription and at three-month intervals thereafter, as well as outreach and counseling services and condom and lubricant promotion and provision.
To judge whether under the various scenarios PrEP is cost-effective, the researchers applied two commonly used but different cost-effectiveness thresholds. The World Health Organization's WHO-CHOICE initiative considers an intervention cost-effective if its cost is less than three times the gross domestic product (GDP) per capita per DALY averted. For Peru, this means an intervention should cost less than US$16,302 per DALY. The World Bank has more stringent criteria: it considers an intervention cost-effective for a middle-income country like Peru if it costs less than US$500 per DALY averted.
The researchers estimate that PrEP is cost-effective in Lima's MSM population for most scenarios by WHO-CHOICE guidelines. Only scenarios that prioritize PrEP to those most likely to become infected (i.e., transwomen at higher risk and sex workers) are cost-effective (and only barely) by the more stringent World Bank criteria. If the savings on antiretroviral drugs to treat people with HIV (those who would have become infected without PrEP) are included in the calculation, most scenarios become cost-effective, even under World Bank criteria.
The most cost-effective scenario, namely, having a modest coverage of 5%, prioritizing PrEP to transwomen at higher risk and sex workers, and assuming fairly high adherence levels among PrEP recipients, is estimated to avert about 8% of new infections among this community over ten years.
What Do these Findings Mean?
These findings suggest that under some circumstances, PrEP could be a cost-effective tool to reduce new HIV infections. However, as the researchers discuss, PrEP is expensive and only partly effective. Moreover, its effectiveness depends on two behavioral factors—adherence to a strict drug regimen and continued practicing of safe sex—both of which remain hard to predict. As a consequence, PrEP alone is not a valid strategy to prevent new HIV infections. It needs instead to be considered as one of several available tools. If and when PrEP is chosen as part of an integrated prevention strategy will depend on the specific target population, the overall funds available, and how well its cost-effectiveness compares with other prevention measures.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001323.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and a section on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV prevention
AVAC Global Advocacy for HIV Prevention provides up-to-date information on HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
The World Health Organization has a page on its WHO-CHOICE criteria for cost-effectiveness
doi:10.1371/journal.pmed.1001323
PMCID: PMC3467261  PMID: 23055836
20.  Exploring the Ethics of Observational Research: The Case of an HIV Study in Tanzania 
AJOB primary research  2012;3(4):30-39.
Background
Observational studies have generally been viewed as incurring minimal risk to participants, resulting in fewer ethical obligations for investigators than intervention studies. In 2004, the lead author (AN) carried out an observational study measuring sexual behavior and the prevalence of HIV, syphilis, and herpes simplex virus type 2 (HSV-2), among Tanzanian agricultural plantation residents (results reported elsewhere). This article uses an ethical lens to consider the consequences of the observational study and explore what, if any, effects it had on participants and their community.
Methods
Using a case study approach, we critically examine three core principles of research ethics—respect for persons/autonomy; beneficence/nonmaleficence; and distributive justice—as manifested in the 2004 observational study. We base our findings on three sources: discussions with plantation residents following presentations of observational research findings; in-depth interviews with key informants; and researcher observations.
Results
The observational research team was found to have ensured confidentiality and noncoercive recruitment. Ironically, maintenance of confidentiality and voluntary participation led some participants to doubt study results. Receiving HIV test results was important for participants and contributed to changing community norms about HIV testing.
Conclusions
Observational studies may act like de facto intervention studies and thus incur obligations similar to those of intervention studies. We found that ensuring respect for persons may have compromised the principles of beneficence and distributive justice. While in theory these three ethical principles have equal moral force, in practice, researchers may have to prioritize one over the others. Careful community engagement is necessary to promote well-considered ethical decisions.
doi:10.1080/21507716.2012.714836
PMCID: PMC3779918  PMID: 24069546
Africa; autonomy; beneficence; cross-sectional; distributive justice; ethics; observational research
21.  Health and Human Rights Concerns of Drug Users in Detention in Guangxi Province, China 
PLoS Medicine  2008;5(12):e234.
Background
Although confinement in drug detoxification (“detox”) and re-education through labor (RTL) centers is the most common form of treatment for drug dependence in China, little has been published about the experience of drug users in such settings. We conducted an assessment of the impact of detention on drug users' access to HIV prevention and treatment services and consequent threats to fundamental human rights protections.
Methods and Findings
Chinese government HIV and anti-narcotics legislation and policy documents were reviewed, and in-depth and key informant interviews were conducted with 19 injection drug users (IDUs) and 20 government and nongovernmental organization officials in Nanning and Baise, Guangxi Province. Significant contradictions were found in HIV and antinarcotics policies, exemplified by the simultaneous expansion of community-based methadone maintenance therapy and the increasing number of drug users detained in detox and RTL center facilities. IDU study participants reported, on average, having used drugs for 14 y (range 8–23 y) and had been confined to detox four times (range one to eight times) and to RTL centers once (range zero to three times). IDUs expressed an intense fear of being recognized by the police and being detained, regardless of current drug use. Key informants and IDUs reported that routine HIV testing, without consent and without disclosure of the result, was the standard policy of detox and RTL center facilities, and that HIV-infected detainees were not routinely provided medical or drug dependency treatment, including antiretroviral therapy. IDUs received little or no information or means of HIV prevention, but reported numerous risk behaviors for HIV transmission while detained.
Conclusions
Legal and policy review, and interviews with recently detained IDUs and key informants in Guangxi Province, China, found evidence of anti-narcotics policies and practices that appear to violate human rights and imperil drug users' health.
Based on their review of Chinese government legislation and policy documents, and using interviews with recently detained injection drug users and officials in Guangxi Province, Elizabeth Cohen and Joseph Amon find evidence of antinarcotics policies and practices that may compromise the health and human rights of drug users.
Editors' Summary
Background.
Ever since the AIDS (acquired immunodeficiency syndrome) epidemic began, needle sharing by injection drug users (IDUs) has been a major transmission route for the human immunodeficiency virus (HIV), the blood-borne virus that causes AIDS. In China, for example, the AIDS epidemic began in earnest in 1989 when 146 HIV-positive IDUs were identified in Southwest Yunnan. By 1998, HIV infections had been reported throughout China, 60%–70% of which were in IDUs. These days, nearly half of new HIV infections in China are associated with injection drug use and 266,000 of the 700,000 HIV-positive people in China are drug users. Faced with these figures, the Chinese government has recently introduced measures to reduce HIV transmission among the estimated 3–4 million IDUs in China. These measures include increased provision of methadone maintenance treatment clinics and needle exchanges and the establishment of HIV prevention programs that target IDUs.
Why Was This Study Done?
Alongside these progressive public-health practices, China has extremely punitive anti-narcotics policies. IDUs are routinely confined without legal review in drug detoxification centers or sent to re-education through labor (RTL) centers, sometimes for many years. In 2005, these centers housed more than 350,000 drug users yet little is known about the conditions in these centers or how the Chinese anti-narcotic policy affects human rights or access to HIV prevention and treatment services. In this study, the researchers investigated these issues by interviewing IDUs and “key informants” (government officials and members of nongovernmental organizations [NGOs] who provide services to IDUs) about their experiences of detoxification centers and RTL centers in two cities in Guangxi Province, China.
What Did the Researchers Do and Find?
The researchers recruited 19 IDUs who had been recently confined in a detoxification center or RTL center and 20 key informants (including a doctor at a detoxification center and a former RTL center guard). In the interviews the researchers used a semi-structured questionnaire to ask the participants about their experiences of detoxification centers and RTL centers. All the IDUs reported that they were repeatedly tested for HIV while in detention but never given their test results even when they asked for them. Key informants confirmed that repeated HIV testing without result disclosure is the current policy in detoxification centers and RTL centers. All the IDUs expressed concerns about inadequate access to health care in detention. In particular, most of the IDUs who were taking antiretroviral drugs before detention were unable to continue their treatment during detention, although two received antiretroviral drugs by negotiating with their guards. The IDUs and key informants also both noted that very little information or means of HIV prevention was provided in the detoxification centers and RTL centers and that HIV-related risk behaviors, including injection drug use and unsafe sex, occurred in both types of center. Finally, the IDUs reported that their fear of being recognized by the police and detained even if not taking drugs prevented them from seeking HIV tests, HIV treatment, and help for their drug addiction.
What Do These Findings Mean?
This study has several limitations in addition to its small size. For example, because the IDUs were self selected—they responded to posters asking if they would be interviewed—their views may not be representative of all IDUs. Similarly, the key informants who were interviewed might have had different opinions from those who chose not to participate. Furthermore, the results reported here cannot be generalized to other areas of China. Nevertheless, the consistent experiences reported by the IDUs and confirmed by the key informants suggest that China's anti-narcotic policies and practices violate the human rights of IDUs and put their health in danger by making it hard for them to access HIV prevention and treatment or adequate treatment for their drug addiction. This situation, if not remedied, is likely to jeopardize China's attempts to control its HIV epidemic.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050234.
This study is further discussed in a PLoS Medicine Perspective by Steve Koester
Avert, an international AIDS charity, provides information on all aspects of HIV/AIDS, including HIV and AIDS in China and HIV prevention, harm reduction, and injecting drug use
The UNAIDS 2008 Country Progress Report provides up-to-date details about the AIDS situation in China
HIVInSite provides links to more information about HIV/AIDS in China.
Human Rights Watch works on health and human rights and human rights developments in China
The US National Institute on Drug Abuse provides a booklet entitled Principles of Drug Addiction Treatment: A Research Based Guide (in English and Spanish)
UN Office on Drugs and Crime has information on HIV/AIDS in prisons
doi:10.1371/journal.pmed.0050234
PMCID: PMC2596857  PMID: 19071954
22.  Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study 
PLoS Medicine  2013;10(10):e1001534.
Using nine structurally different models, Jan Hontelez and colleagues investigate timeframes for HIV elimination in South Africa using a universal test and treat strategy.
Please see later in the article for the Editors' Summary
Background
Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV.
Methods and Findings
We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled.
Conclusions
Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (mostly in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS, and every year another 2.5 million people become infected. HIV, which is usually transmitted through unprotected sex with an infected partner, gradually destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, people infected with HIV often died within ten years of infection. Then, in 1996, antiretroviral therapy (ART) became available, and, for people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive, so HIV/AIDS remained a fatal condition for people living in resource-limited countries. In 2006, the international community set a target of achieving universal ART coverage by 2010, and ART programs were initiated in many resource-limited countries. Although universal ART coverage has still not been achieved in South Africa, where nearly 6 million people are HIV-positive, 80% of people in need of ART were receiving a World Health Organization–recommended ART regimen by October 2012.
Why Was This Study Done?
ART is usually started when a person's CD4 count falls below 350 cells/µl blood, but it is thought that treatment of all HIV-positive individuals, regardless of their CD4 count, could reduce HIV transmission by reducing the infectiousness of HIV-positive individuals (“treatment as prevention”). Might it be possible, therefore, to eliminate HIV by screening everyone annually for infection and treating all HIV-positive individuals immediately? In 2009, a mathematical modeling study suggested that seven years of universal test and treat (UTT) could eliminate HIV in South Africa. The deterministic (nonrandom) model used in that study has been widely criticized, however, and some subsequent modeling studies have reached different conclusions, probably because of differences in the models' structures and in the assumptions built into them. A better understanding of the reasons for the discrepancies between models would help policy-makers decide whether to introduce UTT, so, here, the researchers developed several increasingly complex and realistic models of the South African HIV epidemic and used these models to predict the long-term impact of UTT in South Africa.
What Did the Researchers Do and Find?
The researchers developed nine structurally different mathematical models of the South African HIV epidemic based on the STDSIM framework, a stochastic microsimulation model that simulates the life course of individuals in a dynamic network of sexual contacts and in which events such as HIV infection are random processes. The simplest model, which resembled the original deterministic model, was extended by sequentially adding in factors such as different HIV transmission rates at different stages of HIV infection and up-to-date assumptions regarding the ability of ART to reduce HIV infectiousness. All the models replicated the prevalence of HIV in South Africa (the proportion of the population that was HIV-positive) between 1990 and 2010, and all predicted that UTT (defined as annual screening of individuals age 15+ years and immediate ART for all HIV-infected adults starting in 2012 and scaled up to 90% coverage by 2019) would result in HIV elimination (less than one new infection per 1,000 person-years). However, whereas the simplest model predicted that UTT would eliminate HIV after seven years, the more complex, realistic models predicted elimination at much later time points. Importantly, the most comprehensive model predicted that, although elimination would be reached after about 17 years of UTT, the current strategy of ART initiation for HIV-positive individuals at a CD4 cell count at or below 350 cells/µl would also lead to HIV elimination, albeit ten years later than UTT.
What Do These Findings Mean?
These findings confirm previous predictions that UTT could eliminate HIV in South Africa, but the development of more realistic models than those used in the past suggests that HIV elimination would occur substantially later than originally predicted. Importantly, the most comprehensive model suggests that HIV could be eliminated in South Africa using the current strategy for ART treatment alone. As with all modeling studies, the accuracy of these findings depends on the assumptions built into the models and on the structure of the models. Thus, although these findings support the use of UTT as an intervention to eliminate HIV, more research with comprehensive models that incorporate factors such as data from ongoing trials of treatment as prevention is needed to determine the population-level impact and overall cost-effectiveness of UTT.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001534.
This study is further discussed in a PLOS Medicine Perspective by Ford and Hirnschall
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, on HIV treatment as prevention and the possibility of HIV elimination (in English and Spanish)
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
The World Health Organization provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
The PLOS Medicine Collection Investigating the Impact of Treatment on New HIV Infections provides more information about HIV treatment as prevention
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001534
PMCID: PMC3805487  PMID: 24167449
23.  Impact and Process Evaluation of Integrated Community and Clinic-Based HIV-1 Control: A Cluster-Randomised Trial in Eastern Zimbabwe 
PLoS Medicine  2007;4(3):e102.
Background
HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections (STIs) at the population and individual levels.
Methods and Findings
We measured the feasibility of community-based peer education, free condom distribution, income-generating projects, and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-randomised controlled trial in eastern Zimbabwe. Analysis of primary outcomes was on an intention-to-treat basis. The income-generating projects proved impossible to implement in the prevailing economic climate. Despite greater programme activity and knowledge in the intervention communities, the incidence rate ratio of HIV-1 was 1.27 (95% confidence interval [CI] 0.92–1.75) compared to the control communities. No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities. Males who attended programme meetings had lower HIV-1 incidence (incidence rate ratio 0.48, 95% CI 0.24–0.98), and fewer men who attended programme meetings reported unprotected sex with casual partners (odds ratio 0.45, 95% CI 0.28–0.75). More male STI patients in the intervention communities reported cessation of symptoms (odds ratio 2.49, 95% CI 1.21–5.12).
Conclusions
Integrated peer education, condom distribution, and syndromic STI management did not reduce population-level HIV-1 incidence in a declining epidemic, despite reducing HIV-1 incidence in the immediate male target group. Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups.
In cluster-randomised trial in Zimbabwe integrated peer education, condom distribution, and management of sexually transmitted infections did not reduce incidence of population-level HIV-1.
Editors' Summary
Background.
Sub-Saharan Africa has been hit heavily by HIV/AIDS, and Zimbabwe in particular has been very badly affected, with over one-fifth of its adult population infected with HIV. However, this proportion has been declining slowly in recent years, and the same trend has also been seen in a few other African countries. It is not clear whether these trends are related to changes in the way people behave, perhaps as a result of public health and prevention campaigns, or rather are due to changes in the natural spread of the HIV epidemic. However, there is considerable uncertainty about how we should carry out campaigns that try to get people to change their behavior. One possible approach for achieving behavior change involves peer education: that is, education carried out within the community, by at-risk community members themselves. Another approach involves tying together a set of related programs that deliver information and education through health clinics and directly in the community. Such programs are termed “integrated community and clinic-based HIV prevention.”
Why Was This Study Done?
The researchers wanted to find out whether providing integrated community and clinic-based strategies for HIV prevention in Eastern Zimbabwe could reduce the proportion of people within the community infected with HIV. If successful, then the strategies could be effective elsewhere, for example in other African countries where behavior patterns and the HIV epidemic are similar to the situation studied here.
What Did the Researchers Do and Find?
The research was done as a cluster-randomized trial. This means that different communities were assigned by chance to one of two trial arms, either an “intervention arm”, where the community and clinic-based strategies would be delivered, or a “control” arm which would not have additional services. Six pairs of communities in Eastern Zimbabwe were compared, each of which had its own health center. Control communities received the standard government services for preventing HIV. The other communities received a package of various additional strategies. These included education and condom distribution amongst sex workers and their clients; better services at sexually transmitted infection (STI) clinics (STIs can increase the risk of HIV infection); and educational HIV/AIDS open days at health centers. The researchers planned to compare, between the two arms, the number of people who became infected with HIV over the course of the trial. They found that there was no statistical difference in the number of people in the intervention arm who became infected with HIV over the course of the trial, as compared to people in the control arm. Men in the intervention communities were more likely to have effective treatment for STIs, but women were more likely to show risky behaviors, such as having sex at a younger age, and having unprotected sex. However, men in the intervention communities were more knowledgeable about HIV/AIDS than men in the control communities. One strategy in the intervention arm (delivery of education and condom distribution among sex workers and their clients) may have been less successful because of the economic situation at the time, which meant that the income-generating projects that were supposed to support this initiative were impossible.
What Do These Findings Mean?
Some of the results from this trial are encouraging, for example an improvement in male participants' knowledge and behavior. However, overall, the intervention did not have an impact on the HIV infection rate in the community. Some other trials have also shown similar results. These results mean that other strategies need to be developed, and tested, which will encourage people to change their behavior patterns and reduce the risk of getting HIV. However, trials such as this are very difficult to design, carry out, and interpret. In particular, if a complex intervention such as this fails, it is often hard to tell whether it did so because the intervention was not delivered successfully, or because it did not work.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040102.
Information from Avert, an international HIV/AIDS charity, on HIV and AIDS in Zimbabwe
Information from UNAIDS, the United Nations Programme on HIV/AIDS, on strategies for HIV prevention
HIV/AIDS minisite from the World Health Organization
The Web site of the Manicaland HIV/STD Prevention Project discusses this project
doi:10.1371/journal.pmed.0040102
PMCID: PMC1831737  PMID: 17388666
24.  Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis 
PLoS Medicine  2015;12(11):e1001898.
Background
The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.
Methods and Findings
As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.
Conclusions
The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.
Daniela Bezemer and colleagues investigate the extent to which the resurgent HIV epidemic in the Netherlands is the result of newly introduced strains, or of growth of already circulating strains.
Editors' Summary
Background
Since the first recorded case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. Now, three and a half decades later, about 35 million people (more than half of whom are women) are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner, and, globally, most sexual transmission of HIV occurs during heterosexual sex. Nevertheless, many new HIV infections still occur in men who have sex with men (MSM; homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men), and, in some countries, HIV/AIDS still predominantly affects the MSM community. In the US, for example, 78% of new HIV infections occurred among MSM in 2010 although MSM represent only 4% of the total population, and, in 2011, 54% of all people living with HIV were MSM. Indeed, despite HIV-positive individuals being diagnosed earlier these days and having access to effective combination antiretroviral therapy (cART), which both halts disease progression and reduces the risk of HIV transmission, the HIV epidemic among MSM is resurgent (growing again) in many Western countries.
Why Was This Study Done?
To control this resurgent epidemic, it is important to know as much as possible about HIV transmission among MSM so that effective prevention strategies can be designed. Here, the researchers use phylogenetic analysis and mathematical modeling to ask whether the introduction of new strains or the spread of already circulating strains is responsible for the resurgent HIV-1 subtype B epidemic occurring among MSM in the Netherlands. Viral phylogenetic analysis infers evolutionary relationships between viral strains by examining their genetic relatedness and can be used to identify HIV transmission clusters. HIV-1 viruses are classified into subtypes based on their genetic sequence and geographical distribution. HIV-1 subtype B is a common subtype that is found in west and central Europe, the Americas, and several other regions.
What Did the Researchers Do and Find?
The researchers built a phylogenetic tree for the HIV epidemic in MSM in the Netherlands by analyzing HIV-1 subtype B polymerase gene sequences found in 5,852 participants (73% of whom were MSM) in the ATHENA cohort, an observational cohort of all HIV-1-infected patients in care in the Netherlands since 1996 (when cART became available). Examination of this tree identified 106 large transmission clusters (groups of ten or more closely related subtype B HIV-1 strains). Half of the HIV-1 polymerase sequences from HIV-1-positive MSM registered in the ATHENA cohort in the Netherlands were included in 91 MSM-majority clusters: large transmission clusters in which more than half the related sequences originated from MSM. At least 54 of the MSM-majority clusters were circulating before 1996 and have persisted until the present day. Moreover, about a third of new HIV infections diagnosed among MSM since 1996 involve viruses included in these long-lived clusters. The researchers then used mathematical modeling to estimate that the effective reproduction number (the number of secondary infections per primary infection) for all the MSM-majority clusters was around one for the whole study period. Thus, these clusters were self-sustaining and not contracting. Notably, MSM-majority clusters (particularly the newer clusters) tended to have higher reproduction numbers in recent years. Moreover, although the average age at diagnosis within each of the MSM-majority clusters increased over the study period at a rate of 0.45 years/year, the average age at diagnosis was lower at initiation of new clusters and only increased by 0.28 years/year.
What Do These Findings Mean?
These findings suggest that several large, persistent, and self-sustaining sub-epidemics, many of which have been present since early in the AIDS epidemic, are driving the resurgent HIV epidemic among MSM in the Netherlands, despite the widespread availability of treatment, increasing rates of diagnosis, and earlier treatment initiation. Importantly, however, these findings also suggest that some sub-epidemics have emerged more recently and that some sub-epidemics, particularly the newer ones, are growing and may be preferentially affecting younger MSM. The accuracy of these findings may be limited by some aspects of the study. For example, the reproduction number estimates assume that the time from diagnosis of a case to the diagnoses of secondary cases is similar across clusters. Nevertheless, the new insights provided by this study should help guide the development of strategies to curb the resurgent HIV epidemic that is currently affecting MSM in the Netherlands and elsewhere.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001898.
The US Centers for Disease Control and Prevention provides information on all aspects of HIV/AIDS, including information on HIV/AIDS among MSM (in English and Spanish)
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings, including information on HIV and MSM and personal stories from MSM living with HIV
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including MSM and HIV; Avert also provides personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS, including HIV/AIDS and MSM (in several languages)
The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it
A 2011 World Bank Report The Global HIV Epidemics among Men Who Have Sex with Men is available
A PLOS Computational Biology Topic Page (a review article that is a published copy of record of a dynamic version of an article in Wikipedia) about viral phylodynamics is available
doi:10.1371/journal.pmed.1001898
PMCID: PMC4631366  PMID: 26529093
25.  Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts 
PLoS Medicine  2015;12(3):e1001801.
Background
The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk.
Methods and Findings
We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own.
From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79–57) and dacute = 1.7 mo (95% CrI: 0.55–6.8). The wide credibility intervals reflect an inability to distinguish a long, mildly infectious acute phase from a short, highly infectious acute phase, given the 10-mo Rakai observation intervals. The total additional risk, measured as excess hazard-months attributable to the acute phase (EHMacute) can be estimated more precisely: EHMacute = (RHacute - 1) × dacute, and should be interpreted with respect to the 120 hazard-months generated by a constant untreated chronic phase infectivity over 10 y of infection. From the Rakai data, we estimated that EHMacute = 8.4 (95% CrI: -0.27 to 64). This estimate is considerably lower than previously published estimates, and consistent with our independent estimate from viral load trajectories, 5.6 (95% confidence interval: 3.3–9.1). We found that previous overestimates likely stemmed from failure to account for risk heterogeneity and bias resulting from the retrospective cohort study design.
Our results reflect the interaction between the retrospective cohort exclusion criteria and high (47%) rates of censorship amongst incident serodiscordant couples in the Rakai study due to loss to follow-up, couple dissolution, or study termination. We estimated excess physiological infectivity during the acute phase from couples data, but not the proportion of transmission attributable to the acute phase, which would require data on the broader population's sexual network structure.
Conclusions
Previous EHMacute estimates relying on the Rakai retrospective cohort data range from 31 to 141. Our results indicate that these are substantial overestimates of HIV-1 acute phase infectivity, biased by unmodeled heterogeneity in transmission rates between couples and by inconsistent censoring. Elevated acute phase infectivity is therefore less likely to undermine TasP interventions than previously thought. Heterogeneity in infectiousness and susceptibility may still play an important role in intervention success and deserves attention in future analyses
Using simulated cohorts that account for previously unmeasured bias, Steve Bellan and colleagues provide new estimates of the duration and relative infectivity of the HIV-1 acute phase based on data from the retrospective cohort of serodiscordant couples in Rakai, Uganda.
Editors' Summary
Background.
About 35 million people are currently infected with HIV, the virus that causes AIDS, and more than 2 million people become newly infected with the virus every year, usually through having unprotected sex with an infected partner. Most people do not become ill immediately after infection, although some people develop a short flu-like illness. However, during this acute phase of infection, the amount of virus in the blood—the viral load—rises rapidly and peaks, before decreasing to a relatively stable lower level during the chronic phase of HIV infection. Chronic HIV infection, which may last for more than ten years, also has no major symptoms, but HIV slowly destroys immune system cells throughout this phase. Eventually, the immune system can no longer fight off infections by other disease-causing organisms, and HIV-positive people then develop one or more AIDS-defining conditions, including unusual infections and specific types of cancer; the HIV load also rises again during late phase infection.
Why Was This Study Done?
Antiretroviral therapy (ART) can control, but not cure, HIV infection. By decreasing the viral load, ART not only improves the health of HIV-positive individuals, but also reduces their infectiousness. Consequently, experts believe that scaling up ART could substantially reduce the rate of new HIV infections. But the successful implementation of “treatment as prevention” faces several challenges. Notably, HIV testing and treatment programs need to be widely available, and people who are HIV-positive need to adhere to ART. Another major challenge that faces treatment as prevention is that HIV transmission that occurs during the acute phase of infection is likely to evade the intervention, and it is widely accepted that HIV-positive individuals are highly infectious during this phase of infection. However, acute phase infectivity has been directly measured only once: in a retrospectively identified group of serodiscordant heterosexual couples (couples in which only one partner was HIV-positive) in Rakai, Uganda. The authors of the current study found that existing estimates of acute phase infectivity failed to take account of important aspects of the Rakai study design or of heterogeneity (variability) in infectiousness or susceptibility among the study participants. Here, the researchers use mathematical modeling to compare simulated cohorts with the Rakai data to provide new estimates of the duration and relative infectivity of the acute phase that take into account study design and heterogeneity.
What Did the Researchers Do and Find?
The researchers first used viral load trajectories and viral load–infectivity relationships to estimate infectivity trajectories over the course of infection. Using this approach, they estimated that the total additional risk attributable to the acute phase expressed as EHMacute (excess hazard-months attributable to the acute phase of infection above the hazard generated by constant untreated chronic phase infectivity) was 5.6, which is considerably lower than previous estimates (which range from 31 to 141). Next, by fitting a mathematical model designed to simulate HIV infection and transmission within couples to the Rakai data, they estimated that the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) was 5.3, that the acute phase duration (dacute) was 1.7 months, and that EHMacute was 8.4. Finally, by replicating two highly cited analyses of the Rakai data on simulated data, the researchers show that the previous overestimates of acute phase infectivity likely stemmed from a failure to account for risk heterogeneity among study participants (some participants were more likely to transmit HIV or contract HIV than others because of underlying biological or behavioral differences in their infectiousness or susceptibility, respectively) and from bias arising from the retrospective cohort design of the Rakai study (serodiscordant couples who were lost to follow-up were excluded).
What Do These Findings Mean?
In common with previous estimates of acute phase infectivity, the accuracy of these findings depends on the many assumptions made by the researchers in developing their mathematical models and on the quality of the data fed into these models. Nevertheless, these findings suggest that previous estimates of the infectivity of acute phase HIV infection are substantial overestimates. Thus, the researchers suggest, elevated infectiousness early in infection alone is unlikely to undermine treatment as prevention campaigns, and the population-level benefits of treatment as prevention may be larger than predicted from earlier estimates. These revised estimates—and the impact of heterogeneity of HIV infectiousness and susceptibility to infection on HIV transmission within populations revealed by this analysis—should now be considered when designing population-scale interventions and when communicating individual-level risk of HIV transmission and infection in clinical and community settings.
Additional Information.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001801.
This study is further discussed in a PLOS Medicine Perspective by Laith J. Abu-Raddad
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, information about transmission and prevention, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including detailed information on the stages of HIV infection and on treatment as prevention, and personal stories about living with HIV/AIDS
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection
The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it
The PLOS Medicine Collection “Investigating the Impact of Treatment on New HIV Infections” provides more information about HIV treatment as prevention
doi:10.1371/journal.pmed.1001801
PMCID: PMC4363602  PMID: 25781323

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