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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.  A Comparison of Voluntary Counseling and Testing Uptake Between a China CARES County and a County Not Designated for the China CARES Program 
AIDS Patient Care and STDs  2008;22(6):521-533.
Abstract
A cross-sectional study employing two-stage cluster sampling was conducted between December 2005 and March 2006 to compare adults' knowledge of HIV/AIDS voluntary counseling and testing (VCT) and the attitudes toward and acceptance of VCT between a county in which a comprehensive HIV/AIDS program, China CARES (CC), was available, and a county where it was not. Information on HIV/AIDS knowledge, awareness of VCT, and attitudes was collected. All participants were given a coupon for free VCT after the cross-sectional interview. Uptake of VCT was measured within 2 months of the interview. More participants in the CC county knew someone infected with HIV, had participated in AIDS-related activities, and/or had heard about China CARES. In the control county, education and income levels were higher, there were fewer minorities, and there was a higher proportion of women. VCT uptake was low. Overall, no significant differences in uptake were found between the two counties. Urban residents of the CC county had higher HIV/AIDS knowledge levels than urban residents of the comparison county (p = 0.002). Residents of the CC county were more discriminative against HIV/AIDS and persons living with HIV/AIDS (PLWHA) and had lower perceptions of risk. The differences may be due to the higher proportion of rural residents in the CC county (p < 0.001). The China CARES program may have had a positive effect on urban areas of Guizhou Province in terms of improving HIV/AIDS and VCT knowledge and reducing discrimination, but had little impact in the rural areas. If the China CARES program is to be successful, it must implement a more effective education program and increase the acceptability of testing.
doi:10.1089/apc.2007.0226
PMCID: PMC2928493  PMID: 18462075
3.  Barriers to the implementation of programs for the prevention of mother-to-child transmission of HIV: A cross-sectional survey in rural and urban Uganda 
Background
Implementation of programs for the prevention of mother-to-child transmission (PMTCT) of HIV faces a variety of barriers and challenges. The assessment of these challenges has generally been conducted in large urban health facilities. As programs expand into rural areas, the potential barriers that may be encountered there also need to be assessed. This study examines potential barriers that might affect the acceptability of interventions for PMTCT in rural and urban settings.
Results
Four hundred and four women at a large urban hospital and three rural clinics that had recently started implementing PMTCT were interviewed. Level of knowledge of MTCT and preference for rapid HIV testing were equally high in both areas, but rural women had a higher tendency to think that they should consult their husbands before testing, with borderline statistical significance (72% vs. 64% p = 0.09). Health facility-based deliveries were significantly lower among mothers in rural areas compared to those in the urban setting. Overall, significant predictors of willingness to test for HIV were post-primary education (OR = 3.1 95% CI 1.2, 7.7) and knowledge about rapid HIV tests (OR = 1.8, 95% CI 1.01, 3.4). The strongest predictor of willingness to accept an HIV test was the woman's perception that her husband would approve of her testing for HIV. Women who thought their husbands would approve were almost six times more likely to report a willingness to be tested compared to those who thought their husbands would not approve (OR = 5.6, 95% CI 2.8, 11.2).
Conclusion
Lessons learned in large urban hospitals can be generalized to rural facilities, but the lower proportion of facility-based deliveries in rural areas needs to be addressed. Same-day results are likely to ensure high uptake of HIV testing services but male spousal involvement should be considered, particularly for rural areas. Universal Primary Education will support the success of PMTCT programs.
doi:10.1186/1742-6405-2-10
PMCID: PMC1277814  PMID: 16255776
4.  HIV-related knowledge, stigma, and willingness to disclose: A mediation analysis 
AIDS care  2006;18(7):717-724.
Increasing HIV knowledge is a focus of many HIV education and prevention efforts. While the bivariate relationship of HIV serostatus disclosure with HIV-related knowledge and stigma has been reported in the literature, little is known about the mediation effect of stigma on the relationship of HIV knowledge with HIV serostatus disclosure. Data from 4,208 rural-to-urban migrants in China were analyzed to explore this issue. Overall, 70% of respondents reported willingness to disclose their HIV status if they were HIV-positive. Willingness to disclose was negatively associated with misconceptions about HIV transmission and stigma. Stigma mediated the relationship between misconceptions and willingness to disclose among women but not men. The mediation effect of stigma suggests that stigmatization reduction would be an important component of HIV prevention approaches. Gender inequality needs to be addressed in stigmatization reduction efforts.
doi:10.1080/09540120500303403
PMCID: PMC1933389  PMID: 16971280
5.  Assessment of utilization of provider-initiated HIV testing and counseling as an intervention for prevention of mother to child transmission of HIV and associated factors among pregnant women in Gondar town, North West Ethiopia 
BMC Public Health  2012;12:226.
Background
Detection of maternal HIV infection early in pregnancy is critical for prevention of mother to child transmission of HIV/AIDS. Most efforts have focused on VCT as the primary means of encouraging people to become aware of their HIV status. However, its uptake is low in many parts of sub-Saharan Africa including Ethiopia. Provider-initiated HIV testing and counseling provides a critical opportunity to diagnose HIV infection, to begin chronic care, and to prevent mother to child transmission. However, little is known about its acceptance and associated factors among pregnant women in the country and particularly in the present study area.
Methods
Health institution based cross-sectional quantitative study was conducted in Gondar town from July 22-August 18, 2010. A total of 400 pregnant women were involved in the study using stratified sampling technique and multiple logistic regression analysis was employed using SPSS version 16.
Results
A total of 400 pregnant women actively participated in this study and 330 (82.5%) of them accepted provider-initiated HIV testing and counseling to be tested for HIV and 70(17.5%) of them refused. Acceptance of provider-initiated HIV testing and counseling was positively associated with greater number of antenatal care visits [Adj. OR (95%CI)=2.64(1.17, 5.95)], residing in the urban areas[Adj. OR (95%CI)=2.85(1.10, 7.41)], having comprehensive knowledge on HIV [Adj. OR (95%CI)=4.30(1.72, 10.73)], positive partners reaction for HIV positive result [Adj. OR (95%CI)=8.19(3.57, 18.80)] and having knowledge on prevention of mother to child transmission of HIV[Adj. OR (95%CI)=3.27(1.34, 7.94)], but negatively associated with increased maternal age and education level.
Conclusion
Utilization of provider-initiated HIV testing and counseling during antenatal care was relatively high among pregnant women in Gondar town. Couple counseling and HIV testing should be strengthened to promote provider-initiated HIV testing and counseling among male partners and to reduce HIV related violence of women from their partner and access to and consistent use of antenatal care should be improved to increase the uptake of provider-initiated HIV testing and counseling service.
doi:10.1186/1471-2458-12-226
PMCID: PMC3350437  PMID: 22440018
6.  The Uptake and Accuracy of Oral Kits for HIV Self-Testing in High HIV Prevalence Setting: A Cross-Sectional Feasibility Study in Blantyre, Malawi 
PLoS Medicine  2011;8(10):e1001102.
Augustine Choko and colleagues assess the uptake and acceptability of home-based supervised oral HIV self-testing in Malawi, demonstrating the feasibility of this approach in a high-prevalence, low-income environment.
Background
Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective.
Methods and Findings
Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test “not hard at all to do,” 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001).
Conclusions
Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to the World Health Organization, despite the dramatic increase in the acceptability of HIV testing, more than 60% of people living with HIV do not know their status—a factor that is seriously hampering the global response to the HIV epidemic. The inconvenience and cost involved in visiting services in addition to a general aversion to visiting health facilities appear to be major barriers. Home-based HIV-testing services bypass these obstacles and are being adopted as national policy in a number of countries. However, given the tension between confidentiality and convenience, many people do not want to be counseled and tested by someone they know well, thus creating logistical difficulties and added costs to the provision of home-based testing services.
Why Was This Study Done?
Self-testing in private has considerable potential to contribute to first-time and repeat HIV testing but raises a number of issues, such as accuracy, the potential for adverse psychological reactions in the absence of face-to-face counseling, and the difficulty in organizing subsequent links to HIV/AIDS care. Self-testing has been used for over a decade in the US, but given the need to further scale up HIV testing and counseling in Africa, and to encourage regular repeat testing, the researchers conducted a mixed quantitative and qualitative study of self-testing for HIV using oral test kits to test whether supervised oral self-testing could yield accurate results. The researchers also wanted to explore reasons for accepting self-testing and respondents' preferences for HIV testing.
What Did the Researchers Do and Find?
The researchers conducted their study in four community health worker catchment areas in three high-density residential suburbs of Blantyre, Malawi. Between March and July 2010, the researchers randomly selected two groups of participants from within these catchment areas and all adults were then invited to participate in interview and optional HIV testing and counseling carried out in their home. Participants were offered the choice between self-test for HIV followed by standard voluntary counseling and testing, standard voluntary counseling and testing only, and no HIV testing or counseling. Pre-and post-test counseling was provided to all participants and after self-testing, a counselor reread the self-test kit, completed a checklist of potential errors and confirmed the result using two rapid HIV test kits run in parallel from a finger-prick blood specimen. All participants testing positive were referred to the nearest primary health center.
All 260 participants who consented to voluntary counseling and testing also opted to self-test, with the remaining 23 (8.1%) choosing not to test. HIV prevalence was 18.5% (48 of 260) and HIV prevalence among participants who had previously tested HIV-negative or not tested at all was 12.0% (29 of 241 participants) meaning that less than half of HIV-infected participants were previously diagnosed, and just over half of undiagnosed HIV infections were in individuals who had previously tested HIV negative. The researchers found self-testing to be highly accurate, with clear and concordant results for 256 (99.2%) of 258 participants with both self-test and blood results. Overall sensitivity for self-test self-read was 97.9% with specificity of 100%. At exit interview, 256 (98.5%) of participants rated self-testing as “very easy” to do but additional help was requested by 26 (10%) of self test participants and procedural errors were identified for 26 participants (10%). Importantly, self-testing was the preferred option for future HIV tests for 56.4% of participants and the most common choice for both men and women.
What Do These Findings Mean?
The findings of this study show that self-testing for HIV (after a brief demonstration and illustrated instructions) is highly accurate and is widely accepted by the community, indicating that there is strong community readiness to adopt self-testing alongside other HIV counseling and testing strategies in high HIV prevalence settings in urban Africa. Self-testing may prove especially valuable for encouraging regular repeat testing, couple testing, and first-time testing in otherwise hard-to-reach groups such as men and older individuals. Finally, given the accuracy achieved and strong preferences around future testing, further exploration of self-testing options could help to make progress towards meeting universal access goals.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001102.
This study is further discussed in a PLoS Medicine Perspective by Walensky and Bassett
Recently published WHO Guidelines explain the principles and processes of adapting HIV guidelines into national programs
The U.S. Centers for Disease Control's initiative Act against AIDS has some user-friendly information on the different types of HIV tests available
A WHO document discusses existing practices and surrounding issues related with HIV self-testing among health workers in sub-Saharan Africa
doi:10.1371/journal.pmed.1001102
PMCID: PMC3186813  PMID: 21990966
7.  Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples 
PLoS Medicine  2012;9(6):e1001251.
In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.
Background
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
Conclusions
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
Trial Registration: ClinicalTrials.com NCT00194519
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since the first reported case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. By the end of 2010, 34 million people were living with HIV/AIDS. At the beginning of the epidemic more men than women were infected with HIV. Now, however, 50% of all adults infected with HIV are women and in sub-Saharan Africa, where two-thirds of HIV-positive people live, women account for 59% of people living with HIV. Moreover, among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because most people in sub-Saharan Africa contract HIV through unprotected heterosexual sex. The risk of HIV transmission for both men and women in Africa and elsewhere can be reduced by abstaining from sex, by only having one or a few partners, by always using condoms, and by male circumcision. In addition, several studies suggest that antiretroviral therapy (ART) greatly reduces HIV transmission.
Why Was This Study Done?
Unfortunately, in sub-Saharan Africa, only about a fifth of HIV-positive people are currently receiving ART, which means that there is an urgent need to find other effective ways to reduce HIV transmission in this region. In this prospective cohort study (a type of study that follows a group of people for some time to see which personal characteristics are associated with disease development), the researchers investigate whether bacterial vaginosis—a condition in which harmful bacteria disrupt the normal vaginal flora—increases the risk of female-to-male HIV transmission among African couples. Bacterial vaginosis, which is extremely common in sub-Saharan Africa, has been associated with an increased risk of HIV acquisition in women and induces viral replication and shedding in the vagina in HIV-positive women, which may mean that HIV-positive women with bacterial vaginosis are more likely to transmit HIV to their male partners than women without this condition. If this is the case, then interventions that reduce the incidence of bacterial vaginosis might be valuable HIV prevention strategies.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 2,236 heterosexual African couples enrolled in a clinical trial (the Partners in Prevention HSV/HIV Transmission Study) whose primary aim was to investigate whether suppression of herpes simplex virus infection could prevent HIV transmission. In all the couples, the woman was HIV-positive and the man was initially HIV-negative. The female partners were examined every three months for the presence of bacterial vaginosis and the male partners were tested regularly for HIV infection. The researchers also determined whether the men who became HIV-positive were infected with the same HIV strain as their partner to check that their infection had been acquired from this partner. The HIV incidence in men whose partners had bacterial vaginosis was 2.9 per 100 person-years (that is, 2.9 out of every 100 men became HIV-positive per year) whereas the HIV incidence in men whose partners had a normal vaginal flora was 0.76 per 100 person-years. After controlling for factors that might affect the risk of HIV transmission such as male circumcision and viral levels in female partner's blood, the researchers estimated that bacterial vaginosis was associated with a 3.17-fold increased risk of female-to-male HIV transmission in their study population.
What Do These Findings Mean?
These findings suggest that HIV-positive African women with bacterial vaginosis are more than three times as likely to transmit HIV to their male partners as those with a normal vaginal flora. It is possible that some unknown characteristic of the men in this study might have increased both their own risk of HIV infection and their partner's risk of bacterial vaginosis. Nevertheless, because bacterial vaginosis is so common in Africa (half of the women in this study had bacterial vaginosis at least once during follow-up) and because this condition is associated with both female HIV acquisition and transmission, these findings suggest that bacterial vaginosis could be responsible for a substantial proportion of new HIV infections in Africa. Normalization of vaginal flora in HIV-infected women by frequent presumptive treatment with antimicrobials (treatment with a curative dose of antibiotics without testing for bacterial vaginosis) or possibly by treatment with probiotics (live “good” bacteria) might, therefore, reduce female-to-male HIV transmission 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.1001251.
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS and on bacterial vaginosis
The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish)
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, and information on bacterial vaginosis and HIV transmission (in several languages)
Information is available from Avert, an international AIDS nonprofit group on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, on women, HIV and AIDS and on HIV/AIDS in Africa (in English and Spanish); personal stories of women living with HIV are available; the website Healthtalkonline also provides personal stories about living with HIV
More information about the Partners in Prevention HSV/HIV Transmission Study is available
doi:10.1371/journal.pmed.1001251
PMCID: PMC3383741  PMID: 22745608
8.  Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study 
PLoS Medicine  2014;11(5):e1001649.
Rashida Ferrand and colleagues combine quantitative and qualitative methods to investigate HIV prevalence among older children receiving primary care in Harare, Zimbabwe, and reasons why providers did not pursue testing.
Please see later in the article for the Editors' Summary
Background
There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children.
Methods and Findings
Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive.
Conclusions
The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over 3 million children globally are estimated to be living with HIV (the virus that causes AIDS). While HIV infection is most commonly spread through unprotected sex with an infected person, most HIV infections among children are the result of mother-to-child HIV transmission during pregnancy, delivery, or breastfeeding. Mother-to-child transmission can be prevented by administering antiretroviral therapy to mothers with HIV during pregnancy, delivery, and breast feeding, and to their newborn babies. According to a report by the Joint United Nations Programme on HIV/AIDS published in 2012, 92% of pregnant women with HIV were living in sub-Saharan Africa and just under 60% were receiving antiretroviral therapy. Consequently, sub-Saharan Africa is the region where most children infected with HIV live.
Why Was This Study Done?
If an opportunity to prevent mother-to-child transmission around the time of birth is missed, diagnosis of HIV infection in a child or adolescent is likely to depend on HIV testing in health care facilities. Health care provider–initiated HIV testing and counselling (PITC) for children is important in areas where HIV infection is common because earlier diagnosis allows children to benefit from care that can prevent the development of advanced HIV disease. Even if a child or adolescent appears to be in good health, access to care and antiretroviral therapy provides a health benefit to the individual over the long term. The administration of HIV testing (and counselling) to children relies not only on health care workers (HCWs) offering HIV testing but also on parents or guardians consenting for a child to be tested. However, more than 30% of children in countries with severe HIV epidemics are AIDS orphans, and economic conditions in these countries cause many adults to migrate for work, leaving children under the care of extended families. This study aimed to investigate the reasons for acceptance and rejection of PITC in primary health care settings in Harare, Zimbabwe. By exploring HCW perspectives on providing HIV testing to children and adolescents, the study also sought to gain insight into factors that could be hindering implementation of testing procedures.
What Did the Researchers Do and Find?
The researchers identified all children aged 6 to 15 years old at six primary care clinics in Harare, who were offered HIV testing as part of routine care between 22 January and 31 May 2013. Study fieldworkers collected data on numbers of child attendances, numbers offered testing, numbers who underwent HIV testing, and reasons why HIV testing did not occur. During the study 2,831 children attending the health clinics were eligible for PITC, and just over half (1,534, 54.2%) underwent HIV testing. Eighty-two children tested HIV-positive, and nearly all of them received counselling, medication, and follow-up care. HCWs offered the test to around 75% of those eligible. The most frequent explanation given by HCWs for a diagnostic test not being offered was that the child was accompanied by a guardian not appropriate for providing consent (401 occasions, 59%); Other reasons given were a lack of available counsellors or test kits and counsellors refusing to conduct the test. The likelihood of being offered the test was lower for children not exhibiting symptoms (such as persistent skin problems), older children, or those attending with a male or a younger guardian. In addition, over 100 guardians or parents provided consent but left before the child could be tested.
The researchers also conducted semi-structured interviews with 12 clinic nurses and counsellors (two from each clinic) to explore challenges to implementation of PITC. The researchers recorded the factors associated with testing not taking place, either when offered to eligible children or when HCWs declined to offer the test. The interviewees identified the frequent absence or unavailability of parents or legal guardians as an obstacle, and showed uncertainty or misconceptions around whether testing of the guardian was mandatory (versus recommended) and whether specifically a parent (if one was living) must provide consent. The interviews also revealed HCW concerns about the availability of adequate counselling and child services, and fears that a child might experience maltreatment if he or she tested positive. HCWs also noted long waiting times and test kits being out of stock as practical hindrances to testing.
What Do These Findings Mean?
Prevalence of HIV was high among the children tested, validating the need for PITC in sub-Saharan health care settings. Although 76% of eligible attendees were offered testing, the authors note that this is likely higher than in routine settings because the researchers were actively recording reasons for not offering testing and counselling, which may have encouraged heath care staff to offer PITC more often than usual. The researchers outline strategies that may improve PITC rates and testing acceptance for Zimbabwe and other sub-Saharan settings. These strategies include developing clear laws and guidance concerning guardianship and proxy consent when testing older children for HIV, training HCWs around these policies, strengthening legislation to address discrimination, and increasing public awareness about HIV infection in older children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001649.
This study is further discussed in a PLOS Medicine Perspective by Davies and Kalk
The Joint United Nations Programme on HIV/AIDS publishes an annual report on the global AIDS epidemic, which provides information on progress towards eliminating new HIV infections
The World Health Organization has more information on mother-to-child transmission of HIV
The World Health Organization's website also has information about treatment for children living with HIV
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001649
PMCID: PMC4035250  PMID: 24866209
9.  Determinants of knowledge of HIV status in South Africa: results from a population-based HIV survey 
BMC Public Health  2009;9:174.
Background
Over 30% of women and men in the South African national HIV household of 2005 indicated that they had previously been tested for HIV (of which 91% were aware of their test results). This paper seeks to describe the associations between socio-demographic, behavioural and social characteristics and knowledge of HIV status among a nationally representative population in South Africa.
Methods
A multistage probability sample involving 16395 male and female respondents, aged 15 years or older was selected. The sample was representative of the South African population by age, race, province and type of living area, e.g. urban formal, urban informal, etc. Respondents were interviewed on HIV knowledge, perceptions and behaviour and provided blood for research HIV testing. Bivariate and multivariate logistic regression was used to identify socio-demographic, social and behavioural factors associated with knowledge of HIV status.
Results
From the total sample 27.6% ever and 7.8% knew their HIV status in the past 12 months. In multivariate analyses being female, the age group 25 to 34 years old, other than African Black population group (White, Coloured, Asian), higher educational level, being employed, urban residence, awareness of a place nearby where one could be tested for HIV, impact of HIV on the household and having had two of more sexual partners in the past year were associated with knowledge of HIV status. Among HIV positive persons awareness of a place nearby where one could be tested for HIV and impact of HIV on the household were associated knowledge of HIV status, and among HIV negative persons HIV risk behaviour (multiple partners, no condom use), awareness of a place nearby where one could be tested for HIV, higher knowledge score on HIV and knowledge of serodiscordance were associated knowledge of HIV status.
Conclusion
Education about HIV/AIDS and access to HIV counselling and testing (HCT) in rural areas, in particular among the Black African population group needs to be improved, in order to enhance the uptake of HIV counselling and testing services, an essential step for the initiation of treatment.
doi:10.1186/1471-2458-9-174
PMCID: PMC2700104  PMID: 19500373
10.  Prejudice and misconceptions about tuberculosis and HIV in rural and urban communities in Ethiopia: a challenge for the TB/HIV control program 
BMC Public Health  2010;10:400.
Background
In Ethiopia, where HIV and tuberculosis (TB) are very common, little is known about the prejudice and misconceptions of rural communities towards People living with HIV/AIDS (PLHA) and TB.
Methods
We conducted a cross sectional study in Gilgel Gibe Field Research area (GGFRA) in southwest Ethiopia to assess the prejudice and misconceptions of rural and urban communities towards PLHA and TB. The study population consisted of 862 randomly selected adults in GGFRA. Data were collected by trained personnel using a pretested structured questionnaire. To triangulate the findings, 8 focus group discussions among women and men were done.
Results
Of the 862 selected study participants, 750(87%) accepted to be interviewed. The mean age of the respondents was 31.2 (SD ± 11.0). Of the total interviewed individuals, 58% of them were females. More than half of the respondents did not know the possibility of transmission of HIV from a mother to a child or by breast feeding. For fear of contagion of HIV, most people do not want to eat, drink, and share utensils or clothes with a person living with HIV/AIDS. A higher proportion of females [OR = 1.5, (95% CI: 1.0, 2.2)], non-literate individuals [OR = 2.3, (95%CI: 1.4, 3.6)], rural residents [OR = 3.8, (95%CI: 2.2, 6.6)], and individuals who had poor knowledge of HIV/AIDS [OR = 2.8, (95%CI: 1.8, 2.2)] were more likely to have high prejudice towards PLHA than respectively males, literates, urban residents and individuals with good knowledge. Exposure to cold air was implicated as a major cause of TB. Literates had a much better knowledge about the cause and methods of transmission and prevention of TB than non-literates. More than half of the individuals (56%) had high prejudice towards a patient with TB. A larger proportion of females [OR = 1.3, (95% CI: 1.0, 1.9)] and non-literate individuals [OR = 1.4, (95% CI: 1.1, 2.0)] had high prejudice towards patients with TB than males and literate individuals.
Conclusion
TB/HIV control programs in collaboration with other partners should invest more in social mobilization and education of the communities to rectify the widespread prejudice and misconceptions.
doi:10.1186/1471-2458-10-400
PMCID: PMC2909168  PMID: 20604951
11.  Do accurate HIV and antiretroviral therapy knowledge, and previous testing experiences increase the uptake of HIV voluntary counselling and testing? Results from a cohort study in rural Tanzania 
BMC Public Health  2013;13:802.
Background
Despite the introduction of free antiretroviral therapy (ART), the use of voluntary counselling and testing (VCT) services remains persistently low in many African countries. This study investigates how prior experience of HIV and VCT, and knowledge about HIV and ART influence VCT use in rural Tanzania.
Methods
In 2006–7, VCT was offered to study participants during the fifth survey round of an HIV community cohort study that includes HIV testing for research purposes without results disclosure, and a questionnaire covering knowledge, attitudes and practices around HIV infection and HIV services. Categorical variables were created for HIV knowledge and ART knowledge, with “good” HIV and ART knowledge defined as correctly answering at least 4/6 and 5/7 questions about HIV and ART respectively. Experience of HIV was defined as knowing people living with HIV, or having died from AIDS. Logistic regression methods were used to assess how HIV and ART knowledge, and prior experiences of HIV and VCT were associated with VCT uptake, with adjustment for HIV status and socio-demographic confounders.
Results
2,695/3,886 (69%) men and 2,708/5,575 women (49%) had “good” HIV knowledge, while 613/3,886 (16%) men and 585/5575 (10%) women had “good” ART knowledge. Misconceptions about HIV transmission were common, including through kissing (55% of women, 43% of men), or mosquito bites (42% of women, 34% of men).
19% of men and 16% of women used VCT during the survey. After controlling for HIV status and socio-demographic factors, the odds of VCT use were lower among those with poor HIV knowledge (aOR = 0.5; p = 0.01 for men and aOR = 0.6; p < 0.01 for women) and poor ART knowledge (aOR = 0.8; p = 0.06 for men, aOR = 0.8; p < 0.01 for women), and higher among those with HIV experience (aOR = 1.3 for men and aOR = 1.6 for women, p < 0.01) and positive prior VCT experience (aOR = 2.0 for all men and aOR = 2.0 for HIV-negative women only, p < 0.001).
Conclusions
Two years after the introduction of free ART in this setting, misconceptions regarding HIV transmission remain rife and knowledge regarding treatment is worryingly poor, especially among women and HIV-positive people. Further HIV-related information, education and communication activities are urgently needed to improve VCT uptake in rural Tanzania.
doi:10.1186/1471-2458-13-802
PMCID: PMC3844310  PMID: 24007326
HIV; VCT; HIV testing; Tanzania; Cohort study
12.  Prevalence and drivers of HIV stigma among health providers in urban India: implications for interventions 
Journal of the International AIDS Society  2013;16(3Suppl 2):18717.
Introduction
HIV stigma inflicts hardship and suffering on people living with HIV (PLHIV) and interferes with both prevention and treatment efforts. Health professionals are often named by PLHIV as an important source of stigma. This study was designed to examine rates and drivers of stigma and discrimination among doctors, nurses and ward staff in different urban healthcare settings in high HIV prevalence states in India.
Methods
This cross-sectional study enrolled 305 doctors, 369 nurses and 346 ward staff in both governmental and non-governmental healthcare settings in Mumbai and Bengaluru, India. The approximately one-hour long interviews focused on knowledge related to HIV transmission, personal and professional experiences with PLHIV, instrumental and symbolic stigma, endorsement of coercive policies, and intent to discriminate in professional and personal situations that involve high and low risk of fluid exposure.
Results
High levels of stigma were reported by all groups. This included a willingness to prohibit female PLHIV from having children (55 to 80%), endorsement of mandatory testing for female sex workers (94 to 97%) and surgery patients (90 to 99%), and stating that people who acquired HIV through sex or drugs “got what they deserved” (50 to 83%). In addition, 89% of doctors, 88% of nurses and 73% of ward staff stated that they would discriminate against PLHIV in professional situations that involved high likelihood of fluid exposure, and 57% doctors, 40% nurses and 71% ward staff stated that they would do so in low-risk situations as well. Significant and modifiable drivers of stigma and discrimination included having less frequent contact with PLHIV, and a greater number of transmission misconceptions, blame, instrumental and symbolic stigma. Participants in all three groups reported high rates of endorsement of coercive measures and intent to discriminate against PLHIV. Stigma and discrimination were associated with multiple modifiable drivers, which are consistent with previous research, and which need to be targeted in future interventions.
Conclusions
Stigma reduction intervention programmes targeting healthcare providers in urban India need to address fear of transmission, improve universal precaution skills, and involve PLHIV at all stages of the intervention to reduce symbolic stigma and ensure that relevant patient interaction skills are taught.
doi:10.7448/IAS.16.3.18717
PMCID: PMC3833193  PMID: 24242265
HIV stigma; stigma drivers; healthcare workers; India
13.  Knowledge and risk behaviors related to HIV/AIDS, and their association with information resource among men who have sex with men in Heilongjiang province, China 
BMC Public Health  2010;10:250.
Backgroud
In Heilongjiang province, the HIV prevalence in men who have sex with men (MSM) is generally lower than other part of China. However, the official perception for their risk of HIV/AIDS infection has been increasing in the province over the years. Moreover, little information on HIV/AIDS was provided to the communities so that we have disadvantage of controlling HIV/AIDS epidemic in the region. The purpose of this study is to investigate the prevalence of HIV among MSM in Heilongjiang province, to assess their knowledge levels and risk behaviors related to HIV/AIDS, and to explore their associations with information resources.
Methods
A cross-sectional study using a standardized questionnaire and blood test was administered in 2008 by local interviewers to a sample (1353) of MSM in four cities in Heilongjiang province.
Results
Among 1353 MSM, 2.3% were identified with HIV infection. About 48.7% of the subjects had multiple male sexual partners and only 37.3% of the subjects had consistent condom use (use every time) in the past 6 months. Most had a fair level of knowledge on HIV/AIDS, with the highest mean knowledge score among the MSM from Jiamusi, those with income 2000-3000 RMB/month, those searching sexual partners via internet and those performed HIV testing over 1 year ago). However, some myths regarding viral transmission (e.g., via mosquito bites or sharing kitchen utensils) also existed. Resources of information from which knowledge and risk behaviors related to HIV/AIDS was most available were television (58.6%) among MSM, followed by sexual partner (51.6%), publicity material (51.0%) and internet (48.7%). Significantly statistical differences of mean knowledge score were revealed in favor of book (P = 0.0002), medical staff (P = 0.0007), publicity material (P = 0.005) and sexual partner (P = 0.02). Press (P = 0.04) and book (P = 0.0003) were contributory to the most frequent condom use (condom use every time), while medical staff (P = 0.005) and publicity material (P = 0.04) is associated with moderate rate of condom use (condom use often).
Conclusions
Although the prevalence of HIV infection is low among MSM in Heilongjiang province, the situation that the risk behaviors were frequent in the population is alarming. The study suggests that some strategies like condom use and education intervention are practical approaches and need to be strengthened.
doi:10.1186/1471-2458-10-250
PMCID: PMC2885333  PMID: 20470385
14.  Knowledge and attitudes towards HIV vaccines among Soweto adolescents 
BMC Research Notes  2008;1:76.
Background
To explore adolescent HIV risk perception, HIV vaccine knowledge, willingness to participate in future HIV vaccine clinical trials, and the factors that influence willingness to participate among high school students in Soweto, South Africa, we recruited school-going youth through randomly selected local high schools. All pupils within the selected schools from whom parental consent and child assent could be obtained were eligible for participation. A self-administered, facilitated questionnaire was completed by all participants.
Findings
Perception of adolescent HIV risk was high. Some misconceptions regarding vaccine research were common, particularly regarding placebo and potential eligibility criteria for prophylactic vaccine trials. Of 240 responses to the willingness item, 84 (35%) indicated they were "probably willing" and 126 (52.5%) that they were "definitely willing to participate". There were no significant differences in willingness by gender, age, school grade, or institution. Factors that were rated as "very important" in determining willingness included receiving current information about HIV research [n = 201 (88.9%)], doing something to honour people who have HIV or have died of AIDS [n = 168 (70.9%)], getting free counselling and testing [n = 167 (70.5)], that participants may receive some protection against HIV infection from the vaccine [n = 160 (70.2%)], and improving motivation to avoid risky behaviour [n = 134 (59%)].
Conclusion
Soweto school-going youth report high degrees of willingness to participate in HIV vaccine trials. This may be related to the high levels of adolescent HIV risk perception. Whether hypothetical willingness translates to participation will await data from adolescent HIV vaccine trials.
doi:10.1186/1756-0500-1-76
PMCID: PMC2546417  PMID: 18759973
15.  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
16.  Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa 
PLoS Medicine  2013;10(9):e1001511.
Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial.
Please see later in the article for the Editors' Summary
Background
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
Methods and Findings
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants—all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%–100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%–100%) by unannounced pill counts and 97.2% (90.6%–100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.
Conclusions
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people (mostly living in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an HIV-infected partner, destroys immune system cells, leaving infected individuals susceptible to other infections. There is no cure for AIDS, although antiretroviral drugs can hold HIV in check, and there is no vaccine against HIV infection. Individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few low risk sexual partners, and by always using a condom. In addition, antiretroviral drugs can potentially be used in two ways to reduce HIV transmission. First, these drugs could be given to HIV-positive individuals to reduce their infectiousness. Second, antiretroviral drugs could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—pre-exposure prophylaxis (PrEP)—has provided varying levels of protection against HIV infection in randomized controlled trials (RCT; studies that monitor the outcomes of groups of patients randomly assigned to receive different test drugs or a placebo/dummy drug).
Why Was This Study Done?
One hypothesis for the varying efficacy of PrEP in RCTs is differential adherence—differences in whether trial participants took the antiretroviral drugs correctly. Antiretroviral drugs only control HIV infections effectively when they are taken regularly and adherence to antiretroviral PrEP is probably also important for HIV prevention. Here, the researchers investigate adherence to antiretroviral prophylaxis in a substudy within the Partners PrEP Study, a placebo-controlled RCT of oral antiretroviral drugs among nearly 5,000 HIV-uninfected members of serodiscordant couples in East Africa. In serodiscordant couples, only one partner is HIV-positive; 20% of couples in Africa who know their HIV status are serodiscordant. In the Partner PrEP Study, the efficacy of HIV protection with oral antiretroviral drugs was 67%–75%.
What Did the Researchers Do and Find?
The researchers selected a “convenience” sample—a sample is taken non-randomly from a population that is close at hand—of 1,147 HIV-uninfected partners enrolled in Uganda. They used unannounced home-based pill counts (an approach that reduced the chance of participants dumping unused pills to appear more adherent than they actually were) and electronic pill bottle monitoring (a microchip in the medication bottle cap recorded whenever the bottle was opened) to measure PrEP adherence in this cohort. All the participants received adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell below 80%. Fourteen participants, all of whom had been assigned to placebo, became HIV-positive during the adherence substudy. The average adherence to PrEP was 99.1% and 97.2% as measured by unannounced pill counts and by electronic monitoring, respectively. About 7% and 26% of participants had less than 80% adherence as measured by unannounced pill count and electronic monitoring, respectively, during at least one 3-month period of the substudy. Greater than 80% adherence was associated with the first 6 months of PrEP use and polygamous marriage. Adherence less than 80% was associated with report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use. Finally, the adherence intervention (intensified counseling) was well received and in the first unannounced pill count after the intervention, adherence increased to above 80% in 92% of participants.
What Do These Findings Mean?
These findings indicate that the high level of PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high level of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. The findings also suggest that low PrEP adherence is associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Several aspects of the study design may limit the accuracy of these findings. For example, although the adherence measures used here are probably more accurate than participant reports of missed doses and clinic-based pill counts (adherence measures that are often used in RCTs), they are not perfect. Nevertheless, these findings provide further support for the ability of PrEP to prevent HIV acquisition when taken regularly; they suggest that adherence interventions in the implementation setting should address sexual behavior, risk perception, and heavy alcohol use; and they provide data to guide ethical decisions about resource allocation for prevention and treatment of HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001511.
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
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 HIV transmission and prevention and on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda, on HIV prevention, and on PrEP (in English and Spanish)
PrEP Watch provides detailed information about PrEP and links to other resources; it includes personal stories from people who have chosen to use PrEP
More information about the Partners PrEP Study is available
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.1001511
PMCID: PMC3769210  PMID: 24058300
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.  Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE) 
PLoS Medicine  2013;10(9):e1001510.
Amanda Mocroft and colleagues investigate risk factors and health outcomes associated with diagnosis at a late stage of infection in individuals across Europe.
Please see later in the article for the Editors' Summary
Background
Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.
Methods and Findings
LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43).
Conclusions
LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year about 2.5 million people become newly infected with HIV, the virus that causes AIDS. HIV can be transmitted through unprotected sex with an infected partner, from an HIV-positive mother to her unborn baby, or through injection of drugs. Most people do not become ill immediately after infection with HIV although some develop a short influenza-like illness. The next stage of the HIV infection, which may last up to 10 years, also has no major symptoms but, during this stage, HIV slowly destroys immune system cells, including CD4 cells, a type of lymphocyte. Eventually, when the immune system is unable to fight off infections by other disease-causing organisms, HIV-positive people develop AIDS-defining conditions—unusual viral, bacterial, and fungal infections and unusual tumors. Progression to AIDS occurs when any severe AIDS-defining condition is diagnosed, when the CD4 count in the blood falls below 200 cells/mm3, or when CD4 cells account for fewer than 15% of lymphocytes.
Why Was This Study Done?
People need to know they are HIV positive as soon as possible after they become infected because antiretroviral therapy, which controls but does not cure HIV infection, works best if it is initiated when people still have a relatively high CD4 count. Early diagnosis also reduces the risk of onward HIV transmission. However, 40%–60% of HIV-positive individuals in developed countries are not diagnosed until they have a low CD4 count or an AIDS-defining illness. Reasons for such late presentation include fear of discrimination or stigmatization, limited knowledge about HIV risk factors, testing, and treatment together with missed opportunities to offer an HIV test. Policy makers involved in national and international HIV control programs need detailed information about patterns of late presentation before they can make informed decisions about how to reduce this problem. In this study, therefore, the researchers use data collected by the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) to analyze trends in late presentation over time across Europe and in different groups of people at risk of HIV infection and to investigate the clinical consequences of late presentation.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 84,524 individuals participating in more than 20 observational studies that were undertaken in 35 European countries and that investigated outcomes among HIV-positive people. Nearly 54% of the participants were late presenters—individuals who had a CD4 count of less than 350 cells/mm3 or an AIDS-defining illness within 6 months of HIV diagnosis. Late presentation was highest among heterosexual males, in Southern European countries, and among people originating in Africa. Overall, late presentation decreased from 57.3% in 2000 to 51.7% in 2010/11. However, whereas late presentation decreased over time among men having sex with men in Central and Northern Europe, for example, it increased over time among female heterosexuals in Southern Europe. Finally, among the 8,000 individuals who developed a new AIDS-defining illness or died during follow-up, compared to non-late presentation, late presentation was associated with an increased incidence of AIDS/death in all regions of Europe during the first and second year after HIV diagnosis (but not in later years); the largest increase in incidence (13-fold) occurred during the first year after diagnosis in Southern Europe.
What Do These Findings Mean?
These findings indicate that, although late presentation with HIV infection has decreased in recent years, it remains an important issue across Europe and in all groups of people at risk of HIV infection. They also show that individuals presenting late have a worse clinical outlook, particularly in the first and second year after diagnosis compared to non-late presenters. Several aspects of the study design may affect the accuracy and usefulness of these findings, however. For example, some of the study participants recorded as late presenters may have been people who were aware of their HIV status but who chose not to seek care for HIV infection, or may have been seen in the health care system prior to HIV diagnosis without being offered an HIV test. Delayed entry into care and late presentation are likely to have different risk factors, a possibility that needs to be studied further. Despite this and other study limitations, these findings nevertheless suggest that HIV testing strategies that encourage early testing in all populations at risk, that ensure timely referrals, and that improve retention in care are required to further reduce the incidence of late presentation with HIV infection in Europe.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001510.
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 detailed information on the stages of HIV infection and on HIV and AIDS in Europe (in English and Spanish)
The HIV in Europe Initiative has information about strategies to improve earlier diagnosis and access to care in Europe
Information about COHERE, which was established in 2005 to conduct epidemiological research on the prognosis and outcome of HIV-infected people from across Europe, is available; more information on the consensus definition of late presentation used in this study is available through the HIV in Europe initiative
Patient stories about living with HIV/AIDS are available through Avert and through the nonprofit website Healthtalkonline
doi:10.1371/journal.pmed.1001510
PMCID: PMC3796947  PMID: 24137103
19.  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
20.  Acquired immunodeficiency syndrome/human immunodeficiency virus knowledge, attitudes, and practices, and use of healthcare services among rural migrants: a cross-sectional study in China 
BMC Public Health  2014;14:158.
Background
Today’s rapid growth of migrant populations has been a major contributor to the human immunodeficiency virus (HIV) epidemic. However, relatively few studies have focused on HIV/acquired immunodeficiency syndrome (AIDS)-related knowledge, attitudes, and practice among rural-to-urban migrants in China. This cross-sectional study was to assess HIV/AIDS-related knowledge and perceptions, including knowledge about reducing high-risk sex.
Methods
Two-phase stratified cluster sampling was applied and 2,753 rural migrants participated in this study. An anonymous self-administered questionnaire was conducted in Guangdong and Sichuan provinces in 2007. Descriptive analysis was used to present the essential characteristics of the respondents. Chi-square test and multiple logistic regression models were performed to examine the associations between identified demographic factors and high-risk sex, sexually transmitted disease (STD) symptoms, and access to HIV screening services among the seven types of workers.
Results
58.6% of participants were knowledgeable about HIV/AIDS transmission, but approximately 90% had a negative attitude towards the AIDS patients, and that 6.2% had engaged in high-risk sex in the past 12 months. Logistic regression analysis revealed sex, marital status, income, migration and work experience to be associated with high-risk sex. Among the 13.9% of workers who reported having STD symptoms, risk factors that were identified included female gender, high monthly income, being married, daily laborer or entertainment worker, frequent migration, and length of work experience. Only 3% of migrant workers received voluntary free HIV screening, which was positively associated with monthly income and workplace.
Conclusions
HIV/AIDS knowledge, attitudes, and practices among rural migrants in China remain a thorny health issue, and use of healthcare services needs to be improved. Low levels of education and knowledge regarding HIV/AIDS among housekeepers and migrant day laborers result in this population likely being engaged in high-risk sex. Government programs should pay more attention to public education, health promotion and intervention for the control of the HIV/AIDS epidemic in China.
doi:10.1186/1471-2458-14-158
PMCID: PMC3996086  PMID: 24520921
China; AIDS/HIV; Knowledge, Attitude and Practice (KAP) study; Rural migrant workers; High-risk sexual behavior; Health services use
21.  Home-based voluntary HIV counselling and testing found highly acceptable and to reduce inequalities 
BMC Public Health  2010;10:347.
Background
Low uptake of voluntary HIV counselling and testing (VCT) in sub-Saharan Africa is raising acceptability concerns which might be associated with ways by which it is offered. We investigated the acceptability of home-based delivery of counselling and HIV testing in urban and rural populations in Zambia where VCT has been offered mostly from local clinics.
Methods
A population-based HIV survey was conducted in selected communities in 2003 (n = 5035). All participants stating willingness to be HIV tested were offered VCT at home and all counselling was conducted in the participants' homes. In the urban area post-test counselling and giving of results were done the following day whereas in rural areas this could take 1-3 weeks.
Results
Of those who indicated willingness to be HIV tested, 76.1% (95%CI 74.9-77.2) were counselled and received the test result. Overall, there was an increase in the proportion ever HIV tested from 18% before provision of home-based VCT to 38% after. The highest increase was in rural areas; among young rural men aged 15-24 years up from 14% to 42% vs. for urban men from 17% to 37%. Test rates by educational attainment changed from being positively associated to be evenly distributed after home-based VCT.
Conclusions
A high uptake was achieved by delivering HIV counselling and testing at home. The highest uptakes were seen in rural areas, in young people and groups with low educational attainment, resulting in substantial reductions in existing inequalities in accessing VCT services.
doi:10.1186/1471-2458-10-347
PMCID: PMC2902437  PMID: 20553631
22.  Awareness of and Willingness to Use Oral Pre-Exposure Prophylaxis for HIV Prevention among HIV-Serodiscordant Heterosexual Couples: A Cross-Sectional Survey in Xinjiang, China 
PLoS ONE  2013;8(7):e67392.
Objectives
We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP.
Methods
Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP.
Results
Only 10 participants (2.8%) reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6%) reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78, <1000 RMB vs. ≥1000 RMB, 95% confidence interval: 1.36–5.69), perceived likelihood of contracting HIV from HIV-positive partner (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12–6.19), and worrying about being discriminated against by others due to oral PrEP use (adjusted odds ratio  = 9.43, No vs. Yes, 95% confidence interval: 3.78–23.50).
Conclusions
Our results showed HIV-negative partners in HIV-serodiscordant heterosexual couples in China had low awareness of oral PrEP but high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be taken into consideration in future PrEP prevention strategy. In addition, efforts should be made to reduce stigma attached to oral PrEP use, which may increase its acceptability among potential users.
doi:10.1371/journal.pone.0067392
PMCID: PMC3712999  PMID: 23874417
23.  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
24.  Analysis of the immunologic status of a newly diagnosed HIV positive population in China 
BMC Infectious Diseases  2013;13:429.
Background
The immunologic status of a newly diagnosed HIV positive population in the era of antiretroviral therapy in China has not been extensively evaluated. We conducted a cross-sectional survey to evaluate the CD4 counts of newly diagnosed HIV-infected persons and determine the factors influencing these counts in China.
Methods
Two thousand eight hundred and sixty-six newly diagnosed HIV-infected patients from 10 provinces in China were selected during 2009 to 2010. Serum samples were collected to measure CD4 counts by flow cytometry. Demographics and medical histories were recorded. Multivariate logistic regression models were used to analyze factors associated with low CD4 count (<100 cells/mm3) at HIV diagnosis.
Results
Among the 2866 patients, 2159 (75.33%) were male. Mean age was 40 years (range: 18–86 years). The median CD4 count at HIV diagnosis was 83 cells/mm3, 72.02% of the patients had a CD4 count that was ≤200 cells/mm3, 53.98% had CD4 counts <100 cells/mm3. The difference in CD4 counts between males and females was not statistically significant (P=0.469). The median CD4 count differed significantly according to age (P=0.002), province (P<0.001), ethnicity (P<0.001) and HIV transmission route (P<0.001). In multivariate logistic analysis, factors associated with greater odds of low CD4 count at HIV diagnosis included male sex, younger age, HIV transmission route classified as unknown transmission risk, having been diagnosed in provinces Guangxi, Henan, Heilongjiang, Jiangxi, Shanghai and Yunnan.
Conclusions
At the time of HIV diagnosis, a large proportion of HIV-infected patients in China had an initial CD4 count that was consistent with relatively advanced disease. Low CD4 count was associated with male gender, younger age, route of HIV transmission and geographical areas. HIV testing policy that promotes routine testing for HIV infection is needed to facilitate earlier HIV diagnosis.
doi:10.1186/1471-2334-13-429
PMCID: PMC3847234  PMID: 24024658
Human immunodeficiency virus; CD4+T lymphocyte count; China
25.  Willingness to use pre-exposure prophylaxis for HIV prevention among female sex workers: a cross-sectional study in China 
HIV/AIDS (Auckland, N.Z.)  2012;4:149-158.
Background
Pre-exposure prophylaxis (PrEP) is a strategy developed to prevent individuals who are human immunodeficiency virus (HIV)-negative from developing HIV infection. In China, while conducting a clinical trial to investigate the effectiveness and safety of PrEP, we performed this survey to assess the willingness of female sex workers to use PrEP, and identify predictors of this willingness.
Methods
From July 2009 to April 2010, a cross-sectional study was carried out in four provinces of China. We recruited 1611 female sex workers who completed a self-administered survey to assess their awareness of and intention to use PrEP. The survey also canvassed demographic, behavioral, and psychosocial variables. Bivariate and multivariable logistic regression models were fitted to identify predictors of intent to use PrEP.
Results
In total, 69% of the women (95% confidence interval [CI] 66.7–71.3) reported intent to use PrEP, and 12% (95% CI 10.5–13.7) had used drugs in the past to prevent a sexually transmitted infection. Further, 16.5% (95% CI 14.7–18.4) had previously heard of PrEP, and 1.4% (95% CI 0.9–2.1) had used PrEP previously to prevent HIV infection. Multivariate analysis indicated the following significant predictors of intent to use PrEP: Han ethnicity (adjusted odds ratio [AOR] 1.446; P = 0.011), urban residence (AOR 1.302; P = 0.027), knowledge about transmission of HIV/acquired immune deficiency virus syndrome (AIDS, AOR 1.817; P = 0.0007), a history of sexually transmitted infection (AOR 1.830; P < 0.0001), a history of using medication to prevent a sexually transmitted disease (AOR 2.547; P < 0.0001), and willingness to access knowledge about HIV/AIDS (AOR 2.153; P < 0.0001).
Conclusion
The majority of female sex workers reported intent to use PrEP if it is safe and effective. Given that most of the participants had never heard of PrEP before, we strongly recommend that educational materials be developed with detailed introduction of PrEP. The risks and benefits of PrEP use should be fully explained to potential users when promoting PrEP in the future.
doi:10.2147/HIV.S33445
PMCID: PMC3463398  PMID: 23055781
human immunodeficiency virus; infection; pre-exposure prophylaxis; PrEP; willingness; female sex workers

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