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1.  Elevated Risk for HIV Infection among Men Who Have Sex with Men in Low- and Middle-Income Countries 2000–2006: A Systematic Review 
PLoS Medicine  2007;4(12):e339.
Background
Recent reports of high HIV infection rates among men who have sex with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income countries. To investigate the global epidemic of HIV among MSM and the relationship of MSM outbreaks to general populations, we conducted a comprehensive review of HIV studies among MSM in low- and middle-income countries and performed a meta-analysis of reported MSM and reproductive-age adult HIV prevalence data.
Methods and Findings
A comprehensive review of the literature was conducted using systematic methodology. Data regarding HIV prevalence and total sample size was sequestered from each of the studies that met inclusion criteria and aggregate values for each country were calculated. Pooled odds ratio (OR) estimates were stratified by factors including HIV prevalence of the country, Joint United Nations Programme on HIV/AIDS (UNAIDS)–classified level of HIV epidemic, geographic region, and whether or not injection drug users (IDUs) played a significant role in given epidemic. Pooled ORs were stratified by prevalence level; very low-prevalence countries had an overall MSM OR of 58.4 (95% CI 56.3–60.6); low-prevalence countries, 14.4 (95% CI 13.8–14.9); and medium- to high-prevalence countries, 9.6 (95% CI 9.0–10.2). Significant differences in ORs for HIV infection among MSM in were seen when comparing low- and middle-income countries; low-income countries had an OR of 7.8 (95% CI 7.2–8.4), whereas middle-income countries had an OR of 23.4 (95% CI 22.8–24.0). Stratifying the pooled ORs by whether the country had a substantial component of IDU spread resulted in an OR of 12.8 (95% CI 12.3–13.4) in countries where IDU transmission was prevalent, and 24.4 (95% CI 23.7–25.2) where it was not. By region, the OR for MSM in the Americas was 33.3 (95% CI 32.3–34.2); 18.7 (95% CI 17.7–19.7) for Asia; 3.8 (95% CI 3.3–4.3) for Africa; and 1.3 (95% CI 1.1–1.6) for the low- and middle-income countries of Europe.
Conclusions
MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium–high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.
From a systematic review, Chris Beyrer and colleagues conclude that men who have sex with men in the Americas, Asia, and Africa have a markedly greater risk of being HIV-infected than does the general population.
Editors' Summary
Background.
AIDS (acquired immunodeficiency syndrome) first emerged in the early 1980s among gay men living in New York and California. But, as the disease rapidly spread around the world, it became clear that AIDS also affected heterosexual men and women. Now, a quarter of a century later, 40 million people are infected with human immunodeficiency virus (HIV), the organism that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and in sub-Saharan Africa, the region most badly hit by HIV/AIDS, heterosexual transmission predominates. However, globally, 5%–10% of all HIV infections are thought to be in men who have sex with men (MSM, a term that encompasses gay, bisexual, transgendered, and heterosexual men who sometimes have sex with men), and in several high-income countries, including the US, male-to-male sexual contact remains the most important HIV transmission route.
Why Was This Study Done?
In the US, the MSM population is visible and there is considerable awareness about the risks of HIV transmission associated with sex between men. In many other countries, MSM are much less visible. They remain invisible because they fear discrimination, stigmatization (being considered socially unacceptable), or arrest—sex between men is illegal in 85 countries. Consequently, MSM are often under-represented in HIV surveillance systems and in prevention and care programs. If the AIDS epidemic is going to be halted, much more needs to be known about HIV prevalence (the proportion of the population that is infected) among MSM. In this study, the researchers have done a systematic review (a type of research where the results of existing studies are brought together) on published reports of HIV prevalence among MSM in low- and middle-income countries to get a better picture of the global epidemic of HIV in this population.
What Did the Researchers Do and Find?
The researchers found 83 published studies that reported HIV prevalence in 38 low- and middle-income countries in Asia, Africa, the Americas, and Eastern Europe. When the results were pooled—in what statisticians call a meta-analysis—MSM were found to have a 19.3-times greater chance of being infected with HIV than the general population. This is described as a pooled odds ratio (OR) of 19.3. The researchers also did several subgroup analyses where they asked whether factors such as injection drug use (another risk factor for HIV transmission), per capita income, geographical region, or the HIV prevalence in the general population were associated with differential risk (increase in odds) of HIV infection compared to the general population. They found, for example, that in countries where the prevalence of HIV in the general population was very low (less than 1 adult in 1,000 infected) the pooled OR for MSM compared to the general population was 58.4; where it was high (more than 1 adult in 20 infected), the pooled OR for MSM was 9.6.
What Do These Findings Mean?
These findings indicate that MSM living in low- to middle-income countries have a greater risk of HIV infection than the general populations of these countries. The subgroup analyses indicate that the high HIV prevalence among MSM is not limited to any one region or income level or to countries with any specific HIV prevalence or injection drug use level. Although the small number and design of the studies included in the meta-analysis may affect the numerical accuracy of these findings, the clear trend toward a higher HIV prevalence of among MSM suggests that HIV surveillance efforts should be expanded to include MSM in those countries where they are currently ignored. Efforts should also be made to include MSM in HIV prevention programs and to improve the efficacy of these programs by investigating the cultural, behavioral, social, and public policy factors that underlie the high HIV prevalence among MSM. By increasing surveillance, research, and prevention among MSM in low- to middle-income countries, it should be possible to curb HIV transmission in this marginalized population and reduce the global burden of HIV.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040339.
The International Lesbian and Gay Association provides a world legal map on legislation affecting lesbian, gay, bisexual, and transgendered people
The International Gay and Lesbian Human Rights Commission provides a page called Off the Map: How HIV/AIDS Programming is Failing Same-Sex Practicing People in Africa
The American Foundation for AIDS Research (amfAR) has launched their MSM initiative, which is focused on providing support to front-line community groups working on providing services and doing research focused on HIV among MSM in lower income-settings
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, including a list of organizations that provide information for gay men and MSM
Information is available from Avert, an international AIDS charity, on HIV, AIDS, and men who have sex with men
The US Centers for Disease Control and Prevention provides information on HIV/AIDS and on HIV/AIDS among men who have sex with men (in English and Spanish)
doi:10.1371/journal.pmed.0040339
PMCID: PMC2100144  PMID: 18052602
2.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Background
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Conclusions
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001295.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project http://www.healthpolicyproject.com has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
doi:10.1371/journal.pmed.1001295
PMCID: PMC3424253  PMID: 22927800
3.  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
4.  An Intervention to Reduce HIV Risk Behavior of Substance-Using Men Who Have Sex with Men: A Two-Group Randomized Trial with a Nonrandomized Third Group 
PLoS Medicine  2010;7(8):e1000329.
In a randomized trial of a behavioral intervention among substance-using men who have sex with men, aimed at reducing sexual risk behavior, Mansergh and colleagues fail to find evidence of a reduction in risk from the intervention.
Background
Substance use during sex is associated with sexual risk behavior among men who have sex with men (MSM), and MSM continue to be the group at highest risk for incident HIV in the United States. The objective of this study is to test the efficacy of a group-based, cognitive-behavioral intervention to reduce risk behavior of substance-using MSM, compared to a randomized attention-control group and a nonrandomized standard HIV-testing group.
Methods and Findings
Participants (n = 1,686) were enrolled in Chicago, Los Angeles, New York City, and San Francisco and randomized to a cognitive-behavioral intervention or attention-control comparison. The nonrandomized group received standard HIV counseling and testing. Intervention group participants received six 2-h group sessions focused on reducing substance use and sexual risk behavior. Attention-control group participants received six 2-h group sessions of videos and discussion of MSM community issues unrelated to substance use, sexual risk, and HIV/AIDS. All three groups received HIV counseling and testing at baseline. The sample reported high-risk behavior during the past 3 mo prior to their baseline visit: 67% reported unprotected anal sex, and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. The three groups significantly (p<0.05) reduced risk behavior (e.g., unprotected anal sex reduced by 32% at 12-mo follow-up), but were not different (p>0.05) from each other at 3-, 6-, and 12-mo follow-up. Outcomes for the 2-arm comparisons were not significantly different at 12-mo follow-up (e.g., unprotected anal sex, odds ratio = 1.14, confidence interval = 0.86–1.51), nor at earlier time points. Similar results were found for each outcome variable in both 2- and 3-arm comparisons.
Conclusions
These results for reducing sexual risk behavior of substance-using MSM are consistent with results of intervention trials for other populations, which collectively suggest critical challenges for the field of HIV behavioral interventions. Several mechanisms may contribute to statistically indistinguishable reductions in risk outcomes by trial group. More explicit debate is needed in the behavioral intervention field about appropriate scientific designs and methods. As HIV prevention increasingly competes for behavior-change attention alongside other “chronic” diseases and mental health issues, new approaches may better resonate with at-risk groups.
Trial Registration
ClinicalTrials.gov NCT00153361
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS first emerged in the early 1980s among gay men living in the US. As the disease spread around the world, it became clear that AIDS also affects heterosexual men and women. Now, three decades on, more than 30 million people are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and, globally, most sexual transmission of HIV now occurs during heterosexual sex. However, 5%–10% of all new HIV infections still occur in men who have sex with men (MSM, a term that encompasses gay, bisexual, transgendered, and heterosexual men who sometimes have sex with men) and, in several high-income countries, male-to-male sexual contact remains the most important HIV transmission route. In the US, for example, more than half of the approximately 50,000 people who become infected with HIV every year do so through male-to-male sexual contact.
Why Was This Study Done?
In countries where MSM are the group at highest risk of HIV infection, any intervention that reduces HIV transmission in MSM should have a major effect on the overall HIV infection rate. Among MSM, sexual behaviors that increase the risk of HIV infection (for example, not using a condom, having anal sex, having sex with a partner of unknown HIV status, and having sex with many partners) are associated with the use of alcohol and noninjection drugs (for example, inhaled amyl nitrite or poppers) during or shortly before sexual encounters. In this study (Project MIX), the researchers investigate whether a group-based behavioral intervention reduces sexual risk behavior in substance-using MSM.
What Did the Researchers Do and Find?
The researchers recruited substance-using MSM from four US cities who had had risky sex at least once in the past 6 months. Participants were randomized to a cognitive-behavioral intervention or to an attention-control group; a third, nonrandomized group of MSM formed a standard HIV counseling and testing only group. All the groups had HIV counseling and testing at the start of the study and completed a questionnaire about their substance use and sexual risk behavior during their most recent anal sex encounter. The cognitive-behavior group then received six weekly 2-hour group sessions focused on reducing substance use and sexual risk behavior by helping the men change their thinking (cognition) and behavior regarding sexual risk taking. The attention-control group received six group sessions about general MSM issues such as relationships, excluding discussion of substance use, and sexual risk behavior. The participants in both of these groups completed the questionnaire about their substance use and sexual risk behavior again at 3, 6, and 12 months after the group sessions; the participants in the standard HIV counseling and testing group completed the questionnaire again about 5 months after completing the first questionnaire (to control for the time taken by the other two groups to complete the intervention). At baseline, about 67% of the participants reported unprotected anal sex and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. At the 3-month follow-up, the incidence of sexual risk behavior had fallen to about 43% in all three groups; the incidence of substance use during sex had fallen to about 50%. Risk taking and substance use remained at these levels in the intervention and attention-control groups at the later follow-up time points.
What Do These Findings Mean?
These findings suggest that this cognitive-behavioral intervention is no better at reducing sexual risk taking among substance-using MSM than is an unrelated video-discussion group or standard HIV counseling and testing. One explanation for this negative result might be that brief counseling is especially effective with people who are ready for a change such as MSM willing to enroll in an intervention trial of this type. Alternatively, just being in the trial might have encouraged all the participants to self-report reduced risk behavior. Thus, alternative scientific designs and methods might be needed to find behavioral interventions that can effectively reduce HIV transmission among substance-using MSM and other people at high risk of HIV infection. Importantly, however, these findings raise the question of whether more extensive, multilevel interventions or broader lifestyle and positive health approaches (rather than single-level or single-subject behavioral interventions) might be needed to reduce sexual risk behavior among substance-using MSM.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000329.
Information is available from the US Department of Health and Human Services on HIV prevention programs, research, and policy
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, including information on HIV transmission and transmission in gay men and other MSM, on substance abuse and HIV/AIDS, and on safer sex
Information is available from Avert, an international AIDS nonprofit, on all aspects of HIV/AIDS, including information on HIV, AIDS, and men who have sex with men and on drink, drugs, and sex (in English and Spanish)
The US Centers for Disease Control and Prevention also have information for the public and for professionals about HIV/AIDS among men who have sex with men (in English and Spanish)
The US National Institute on Drug Abuse has information on HIV/AIDS and drug abuse, including a resource aimed at educating teenagers about the link between drug abuse and the spread of HIV in the US (in English and Spanish)
doi:10.1371/journal.pmed.1000329
PMCID: PMC2927550  PMID: 20811491
5.  The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study 
PLoS Medicine  2012;9(10):e1001323.
Gabriela Gomez and colleagues developed a mathematical model of the HIV epidemic among men who have sex with men and transwomen in Lima, Peru to explore whether HIV pre-exposure prophylaxis could be a cost-effective addition to existing HIV prevention strategies.
Background
HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.
Methods and Findings
We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.
Conclusions
A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Without a vaccine, the only ways to halt the global HIV epidemic are prevention strategies that reduce transmission of the HIV virus. Up until recently, behavioral strategies such as condom use and reduction of sexual partners have been at the center of HIV prevention. In the past few years, several biological prevention measures have also been shown to be effective in reducing (though not completely preventing) HIV transmission. These include male circumcision, treatment for prevention (giving antiretroviral drugs to HIV-infected people, before they need it for their own health, to reduce their infectiousness) and pre-exposure prophylaxis (or PrEP), in which HIV-negative people use antiretroviral drugs to protect themselves from infection. One PrEP regimen (a daily pill containing two different antiretrovirals) has been shown in a clinical trial to reduce new infections by 44% in of men who have sex with men (MSM). In July 2012, the US Food and Drug Administration approved this PrEP regimen to reduce the risk of HIV infection in uninfected men and women who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. The approval makes it clear that PrEP needs to be used in combination with safe sex practices.
Why Was This Study Done?
Clinical trials have shown that PrEP can reduce HIV infections among participants, but they have not examined the consequences PrEP could have at the population level. Before decision-makers can decide whether to invest in PrEP programs, they need to know about the costs and benefits at the population level. Besides the price of the drug itself, the costs include HIV testing before starting PrEP, as well as regular tests thereafter. The health benefits of reducing new HIV infections are calculated in “disability-adjusted life years” (or DALYs) averted. One DALY is equal to one year of healthy life lost. Other benefits include future savings in lifelong HIV/AIDS treatment for every person whose infection is prevented by PrEP.
This study estimates the potential costs and health benefits of several hypothetical PrEP roll-out scenarios among the community of MSM in Lima, Peru. The scientists chose this community because many of the participants in the clinical trial that showed that PrEP can reduce infections came from this community, and they therefore have some knowledge on how PrEP affects HIV infection rates and behavior in this population. Because the HIV epidemic in Lima is concentrated among MSM, similar to most of Latin America and several other developed countries, the results might also be relevant for the evaluation of PrEP in other places.
What Did the Researchers Do and Find?
For their scenarios, the researchers looked at “high coverage” and “low coverage” scenarios, in which 20% and 5% of uninfected individuals use PrEP, respectively. They also divided the MSM community into those at lower risk of becoming infected and those at higher risk. The latter group consisted of transwomen at higher risk (transsexuals and transvestites with many sexual partners) and male sex workers. In a “uniform coverage” scenario, PrEP is equally distributed among all MSM. “Prioritized scenarios” cover transwomen at higher risk and sex workers preferentially. Two additional important factors for the estimated benefits are treatment adherence (i.e., whether people take the pills they have been prescribed faithfully over long periods of time even though they are not sick) and changes in risk behavior (i.e., whether the perceived protection provided by PrEP leads to more unprotected sex).
The cost estimates for PrEP included the costs of the drug itself and HIV tests prior to PrEP prescription and at three-month intervals thereafter, as well as outreach and counseling services and condom and lubricant promotion and provision.
To judge whether under the various scenarios PrEP is cost-effective, the researchers applied two commonly used but different cost-effectiveness thresholds. The World Health Organization's WHO-CHOICE initiative considers an intervention cost-effective if its cost is less than three times the gross domestic product (GDP) per capita per DALY averted. For Peru, this means an intervention should cost less than US$16,302 per DALY. The World Bank has more stringent criteria: it considers an intervention cost-effective for a middle-income country like Peru if it costs less than US$500 per DALY averted.
The researchers estimate that PrEP is cost-effective in Lima's MSM population for most scenarios by WHO-CHOICE guidelines. Only scenarios that prioritize PrEP to those most likely to become infected (i.e., transwomen at higher risk and sex workers) are cost-effective (and only barely) by the more stringent World Bank criteria. If the savings on antiretroviral drugs to treat people with HIV (those who would have become infected without PrEP) are included in the calculation, most scenarios become cost-effective, even under World Bank criteria.
The most cost-effective scenario, namely, having a modest coverage of 5%, prioritizing PrEP to transwomen at higher risk and sex workers, and assuming fairly high adherence levels among PrEP recipients, is estimated to avert about 8% of new infections among this community over ten years.
What Do these Findings Mean?
These findings suggest that under some circumstances, PrEP could be a cost-effective tool to reduce new HIV infections. However, as the researchers discuss, PrEP is expensive and only partly effective. Moreover, its effectiveness depends on two behavioral factors—adherence to a strict drug regimen and continued practicing of safe sex—both of which remain hard to predict. As a consequence, PrEP alone is not a valid strategy to prevent new HIV infections. It needs instead to be considered as one of several available tools. If and when PrEP is chosen as part of an integrated prevention strategy will depend on the specific target population, the overall funds available, and how well its cost-effectiveness compares with other prevention measures.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001323.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and a section on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV prevention
AVAC Global Advocacy for HIV Prevention provides up-to-date information on HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
The World Health Organization has a page on its WHO-CHOICE criteria for cost-effectiveness
doi:10.1371/journal.pmed.1001323
PMCID: PMC3467261  PMID: 23055836
6.  Epidemiology of HIV/AIDS among non-Hispanic black women in the United States. 
BACKGROUND: HIV/AIDS has emerged as a persistent health threat to black women in the United States. For the past decade, HIV disease has been among the top 10 leading causes of death for this population. METHODS: We analyzed national HIV surveillance data from 29 states with confidential name-based HIV infection reporting that have conducted integrated HIV/AIDS surveillance since at least 1998. We also analyzed AIDS surveillance data from all 50 states and the District of Columbia. RESULTS: In 2002, black women represented 14% of all women in the 29 states whose HIV data were analyzed but 72.3% of annual HIV infection diagnoses among women. In that same year, black women were diagnosed with HIV infection at a rate of 68.7 per 100,000, approximately 23 times the rate for white women (three per 100,000) and four times that for Hispanic women (17.2 per 100,000). Likewise, in 2002, black women represented 13% of all women in the 50 states and the District of Columbia but an estimated 67.8% of new AIDS diagnoses among women. In that same year, black women were diagnosed with AIDS at a rate of 48 per 100,000, approximately 23 times the rate for white women (2.1 per 100,000) and more than four times that for Hispanic women (10.6 per 100,000), CONCLUSIONS: Because black women are disproportionately affected by HIV/AIDS, effective strategies are needed to prevent new HIV infections, to detect HIV infections early and to assure adequate treatment for black women who are infected with HIV.
PMCID: PMC2640642  PMID: 16080453
7.  Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics 
PLoS Medicine  2008;5(3):e50.
Background
The structure of sexual contact networks plays a key role in the epidemiology of sexually transmitted infections, and their reconstruction from interview data has provided valuable insights into the spread of infection. For HIV, the long period of infectivity has made the interpretation of contact networks more difficult, and major discrepancies have been observed between the contact network and the transmission network revealed by viral phylogenetics. The high rate of HIV evolution in principle allows for detailed reconstruction of links between virus from different individuals, but often sampling has been too sparse to describe the structure of the transmission network. The aim of this study was to analyze a high-density sample of an HIV-infected population using recently developed techniques in phylogenetics to infer the short-term dynamics of the epidemic among men who have sex with men (MSM).
Methods and Findings
Sequences of the protease and reverse transcriptase coding regions from 2,126 patients, predominantly MSM, from London were compared: 402 of these showed a close match to at least one other subtype B sequence. Nine large clusters were identified on the basis of genetic distance; all were confirmed by Bayesian Monte Carlo Markov chain (MCMC) phylogenetic analysis. Overall, 25% of individuals with a close match with one sequence are linked to 10 or more others. Dated phylogenies of the clusters using a relaxed clock indicated that 65% of the transmissions within clusters took place between 1995 and 2000, and 25% occurred within 6 mo after infection. The likelihood that not all members of the clusters have been identified renders the latter observation conservative.
Conclusions
Reconstruction of the HIV transmission network using a dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic, with evidence of multiple clusters of transmissions dating to the late 1990s, a period when HIV prevalence is known to have doubled in this population. The quantitative description of the transmission dynamics among MSM will be important for parameterization of epidemiological models and in designing intervention strategies.
Using viral genotype data from HIV drug resistance testing at a London clinic, Andrew Leigh Brown and colleagues derive the structure of the transmission network through phylogenetic analysis.
Editors' Summary
Background.
Human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS), is mainly spread through unprotected sex with an infected partner. Like other sexually transmitted diseases, HIV/AIDS spreads through networks of sexual contacts. The characteristics of these complex networks (which include people who have serial sexual relationships with single partners and people who have concurrent sexual relationships with several partners) affect how quickly diseases spread in the short term and how common the disease is in the long term. For many sexually transmitted diseases, sexual contact networks can be reconstructed from interview data. The information gained in this way can be used for partner notification so that transmitters of the disease and people who may have been unknowingly infected can be identified, treated, and advised about disease prevention. It can also be used to develop effective community-based prevention strategies.
Why Was This Study Done?
Although sexual contact networks have provided valuable information about the spread of many sexually transmitted diseases, they cannot easily be used to understand HIV transmission patterns. This is because the period of infectivity with HIV is long and the risk of infection from a single sexual contact with an infected person is low. Another way to understand the spread of HIV is through phylogenetics, which examines the genetic relatedness of viruses obtained from different individuals. Frequent small changes in the genetic blueprint of HIV allow the virus to avoid the human immune response and to become resistant to antiretroviral drugs. In this study, the researchers use recently developed analytical methods, viral sequences from a large proportion of a specific HIV-infected population, and information on when each sample was taken, to learn about transmission of HIV/AIDS in London among men who have sex with men (MSM; a term that encompasses gay, bisexual, and transgendered men and heterosexual men who sometimes have sex with men). This new approach, which combines information on viral genetic variation and viral population dynamics, is called “molecular phylodynamics.”
What Did the Researchers Do and Find?
The researchers compared the sequences of the genes encoding the HIV-1 protease and reverse transcriptase from more than 2,000 patients, mainly MSM, attending a large London HIV clinic between 1997 and 2003. 402 of these sequences closely matched at least one other subtype B sequence (the HIV/AIDS epidemic among MSM in the UK primarily involves HIV subtype B). Further analysis showed that the patients from whom this subset of sequences came formed six clusters of ten or more individuals, as well as many smaller clusters, based on the genetic relatedness of their HIV viruses. The researchers then used information on the date when each sample was collected and a “relaxed clock” approach (which accounts for the possibility that different sequences evolve at different rates) to determine dated phylogenies (patterns of genetic relatedness that indicate when gene sequences change) for the clusters. These phylogenies indicated that at least in one in four transmissions between the individuals in the large clusters occurred within 6 months of infection, and that most of the transmissions within each cluster occurred over periods of 3–4 years during the late 1990s.
What Do These Findings Mean?
This phylodynamic reconstruction of the HIV transmission network among MSM in a London clinic indicates that the HIV epidemic in this population has been episodic with multiple clusters of transmission occurring during the late 1990s, a time when the number of HIV infections in this population doubled. It also suggests that transmission of the virus during the early stages of HIV infection is likely to be an important driver of the epidemic. Whether these results apply more generally to the MSM population at risk for transmitting or acquiring HIV depends on whether the patients in this study are representative of that group. Additional studies are needed to determine this, but if the patterns revealed here are generalizable, then this quantitative description of HIV transmission dynamics should help in the design of strategies to strengthen HIV prevention among MSM.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050050.
Read a related PLoS Medicine Perspective article
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, including a list of organizations that provide information for gay men and MSM
The US Centers for Disease Control and Prevention provides information on HIV/AIDS and on HIV/AIDS among MSM (in English and Spanish)
Information is available from Avert, an international AIDS charity, on HIV, AIDS, and men who have sex with men
The Center for AIDS Prevention Studies (University of California, San Francisco) provides information on sexual networks and HIV prevention
The US National Center for Biotechnology Information provides a science primer on molecular phylogenetics
UK Collaborative Group on HIV Drug Resistance maintains a database of resistance tests
HIV i-Base offers HIV treatment information for health-care professionals and HIV-positive people
The NIH-funded HIV Sequence Database contains data on genetic sequences, resistance, immunology, and vaccine trials
doi:10.1371/journal.pmed.0050050
PMCID: PMC2267814  PMID: 18351795
8.  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
9.  Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(2):e1001608.
Alison Drake and colleagues conduct a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy and the postpartum period and to compare mother-to-child HIV transmission risk among women with incident versus chronic infection.
Please see later in the article for the Editors' Summary
Background
Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.
Methods and Findings
We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0–4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5–2.1) or postpartum women (HR 1.1, 95% CI 0.6–1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2–3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2–4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.
Conclusions
Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to “high risk” cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, about 3.4 million children younger than 15 years old (mostly living in sub-Saharan Africa) are infected with HIV, the virus that causes AIDS by gradually destroying immune system cells, thereby leaving infected individuals susceptible to other serious infections. In 2012 alone, 230,000 children (more than 700 every day) were newly infected with HIV. Most HIV infections among children are the result of mother-to-child HIV transmission (MTCT) during pregnancy, delivery, or breastfeeding. The rate of MTCT (and deaths among HIV-positive pregnant women from complications related to HIV infection) can be greatly reduced by testing women for HIV infection during pregnancy (antenatal HIV testing), treating HIV-positive women with antiretroviral drugs (ARVs, powerful drugs that control HIV replication and allow the immune system to recover) during pregnancy, delivery, and breastfeeding, and giving ARVs to their newborn babies.
Why Was This Study Done?
The World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed a global plan that aims to move towards eliminating new HIV infections among children by 2015 and towards keeping their mothers alive. To ensure the plan's success, the incidence of HIV (the number of new infections) among women and the rate of MTCT must be reduced by increasing ARV uptake by mothers and their infants for the prevention of MTCT. However, the risk of HIV infection among pregnant women and among women who have recently given birth (postpartum women) is poorly understood because, although guidelines recommend repeat HIV testing during late pregnancy or at delivery in settings where HIV infection is common, pregnant women are often tested only once for HIV infection. The lack of retesting represents a missed opportunity to identify pregnant and postpartum women who have recently acquired HIV and to prevent MTCT by initiating ARV therapy. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a study that uses statistical methods to combine the results of several studies), the researchers estimate maternal HIV incidence during pregnancy and the postpartum period, and compare the risk of MTCT among women with incident (new) and chronic (long-standing) HIV infection.
What Did the Researchers Do and Find?
The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. They used random effects statistical models to estimate the pooled HIV incidence rate and cumulative HIV incidence (the number of new infections per number of people at risk), and the association between pregnancy/postpartum status and HIV incidence and MTCT risk and rates. The pooled HIV incidence rate among pregnant/postpartum women estimated from 19 studies (all from sub-Saharan Africa) that reported HIV incidence rates was 3.8/100 person-years. The pooled cumulative HIV incidence was significantly higher in African countries than in non-African countries (3.6% and 0.3%, respectively; a “significant” difference is one that is unlikely to arise by chance). In the five studies that provided suitable data, the risk of HIV acquisition was similar in pregnant, postpartum, and non-pregnant/non-postpartum women. Finally, among African women, the risk of MTCT was 2.9-fold higher during the postpartum period among those who had recently acquired HIV than among those with chronic HIV infection, and 2.3-fold higher during the pregnancy/postpartum periods combined.
What Do These Findings Mean?
These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections. However, the small number of studies included in this meta-analysis and the use of heterogeneous research methodologies in these studies may limit the accuracy of these findings. Nevertheless, these findings have important implications for the global plan to eliminate HIV infections in children. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001608.
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 children and HIV/AIDS and on the prevention of mother-to-child transmission of HIV (in English and Spanish)
The 2013 UNAIDS World AIDS Day Report provides information about the AIDS epidemic and efforts to halt it; the 2013 UNAIDS Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children; the UNAIDS Believe it. Do it website provides information about the campaign to support the UNAIDS global plan
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, NAM/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001608
PMCID: PMC3934828  PMID: 24586123
10.  Are HIV Epidemics among Men Who Have Sex with Men Emerging in the Middle East and North Africa?: A Systematic Review and Data Synthesis 
PLoS Medicine  2011;8(8):e1000444.
A systematic review by Laith Abu-Raddad and colleagues collates and analyzes the epidemiology of HIV among men who have sex with men in Middle Eastern and North African countries.
Background
Men who have sex with men (MSM) bear a disproportionately higher burden of HIV infection than the general population. MSM in the Middle East and North Africa (MENA) are a largely hidden population because of a prevailing stigma towards this type of sexual behavior, thereby limiting the ability to assess infection transmission patterns among them. It is widely perceived that data are virtually nonexistent on MSM and HIV in this region. The objective of this review was to delineate, for the first time, the evidence on the epidemiology of HIV among MSM in MENA.
Methods and Findings
This was a systematic review of all biological, behavioral, and other related data on HIV and MSM in MENA. Sources of data included PubMed (Medline), international organizations' reports and databases, country-level reports and databases including governmental and nongovernmental organization publications, and various other institutional documents. This review showed that onsiderable data are available on MSM and HIV in MENA. While HIV prevalence continues at low levels among different MSM groups, HIV epidemics appear to be emerging in at least few countries, with a prevalence reaching up to 28% among certain MSM groups. By 2008, the contribution of MSM transmission to the total HIV notified cases increased and exceeded 25% in several countries. The high levels of risk behavior (4–14 partners on average in the last six months among different MSM populations) and of biomarkers of risks (such as herpes simplex virus type 2 at 3%–54%), the overall low rate of consistent condom use (generally below 25%), the relative frequency of male sex work (20%–76%), and the substantial overlap with heterosexual risk behavior and injecting drug use suggest potential for further spread.
Conclusions
This systematic review and data synthesis indicate that HIV epidemics appear to be emerging among MSM in at least a few MENA countries and could already be in a concentrated state among several MSM groups. There is an urgent need to expand HIV surveillance and access to HIV testing, prevention, and treatment services in a rapidly narrowing window of opportunity to prevent the worst of HIV transmission among MSM in the Middle East and North Africa.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS first emerged in the early 1980s among gay men living in the US. But, as the disease rapidly spread, it became clear that AIDS also affects heterosexual men and women. Now three decades on, more than 30 million people are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and, globally, most sexual transmission of HIV now occurs during heterosexual sex. However, 5%–10% of all new HIV infections still occur in men who have sex with men (MSM, a term that encompasses homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men). In some countries, male-to-male sexual contact remains the most important transmission route. Moreover, although the global prevalence of HIV infection (the proportion the world's population infected with HIV) has stabilized, the prevalence of HIV infection among MSM seems to be increasing in multiple countries and new and resurgent HIV epidemics among MSM populations are being frequently reported.
Why Was This Study Done?
In the US and the UK, the MSM population is visible and has helped to raise awareness about the risks of HIV transmission through male-to-male sexual contact. In many other countries, MSM are much less visible, fearing discrimination, stigmatization (being considered socially unacceptable) or arrest. In the Middle East and North Africa (MENA, a geographical region that encompasses countries that share historical, socio-cultural, linguistic and religious characteristics), MSM are the most hidden HIV risk group. Consequently, very little is known about HIV transmission patterns among MSM in MENA. Indeed, it is widely thought that there is virtually no information available on the epidemiology (causes, distribution, and control) of HIV among MSM in this region. In this systematic review and data synthesis, the researchers use predefined search criteria to identify all the published and unpublished data on the epidemiology of HIV among MSM in MENA and combine (synthesize) these data to produce a coherent picture of the HIV epidemic in this potentially key group of people for HIV transmission in this region.
What Did the Researchers Do and Find?
The researchers identified 26 articles and 51 other country-level reports and sources of data that included data on the prevalence of male-to-male sexual contact, HIV transmission, levels of high-risk behavior, and the extent of knowledge about HIV among MSM in MENA. The prevalence of HIV infection among MSM was low in most countries but high in others. For example, the infection rate in Pakistan was 27.6% among one MSM group. Importantly, there was some evidence of increasing HIV prevalence and emerging epidemics among MSM in the region. Thus, by 2008, MSM transmission was responsible for more than a quarter of notified cases of HIV in several countries. Worryingly, MSM were involved in several types of HIV-related high risk behavior. For example, they had, on average, between 4 and 14 sexual partners in the past six months, their rates of consistent condom use were generally below 25% and, in some countries, MSM frequently reported injecting drug use, another common mode of HIV transmission. In addition, 20%–75.5% of MSM exchanged sex for money and contact between MSM and female sex workers and other female sexual partners was often common. Finally, although the level of basic knowledge about HIV/AIDS was high, the level of comprehensive knowledge was limited with a high proportion of MSM perceiving their risk of contracting HIV as low.
What Do These Findings Mean?
These findings indicate that there is considerable and increasing data about HIV transmission and risk behavior among MSM in MENA. However, the quality of this evidence varies greatly. Little has been collected over time in individual populations and, because only the visible part of the MSM populations in many MENA countries has been sampled, these findings may not be representative of all MSM in this region. Nevertheless, these findings suggest that HIV epidemics are emerging among MSM in several MENA countries. Importantly, the high levels of risk behaviors practiced by many MSM in MENA mean that MSM could become the pivotal risk group for HIV transmission in this region in the next decade. There is, therefore, an urgent need to expand HIV surveillance and access to HIV testing, prevention and treatment services among MSM in this region to limit the size of the HIV epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000444.
Information about the status of the HIV epidemic in the Middle East and North Africa can be found in the World Bank/UNAIDS/WHO report Characterizing the HIV/AIDS epidemic in the Middle East and North Africa: Time for strategic action
Information about the global HIV epidemic among men who have sex with men can be found in the World Bank report The Global HIV Epidemics among Men Who Have Sex with Men
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, including information on HIV transmission and transmission in gay men and other MSM and on safer sex
Information is available from Avert, an international AIDS charity, on all aspects of HIV/AIDS, including information on HIV, AIDS and men who have sex with men and on HIV and AIDS prevention (in English and Spanish)
The US Centers for Disease Control and Prevention also have information about HIV/AIDS among men who have sex with men (in English and Spanish)
doi:10.1371/journal.pmed.1000444
PMCID: PMC3149074  PMID: 21829329
11.  HIV/AIDS among minority races and ethnicities in the United States, 1999-2003. 
BACKGROUND: During June 1981 to June 1982, 37% of more than 400 cases of AIDS reported to the CDC were in minority races and ethnicities. In 2003, 72% of the estimated 43,171 cases of AIDS diagnosed in the 50 states; District of Columbia; and U.S. dependencies, possessions and free nations were in minority races and ethnicities. METHODS: We analyzed HIV/AIDS data for 2000-2003 reported by the 32 states that have had confidential name-based reporting of HIV infection since 1999. For analysis of AIDS data, we used data for 1999-2003 reported by the 50 states and the District of Columbia. HIV/AIDS and AIDS data were statistically adjusted for reporting delays and redistribution of cases initially reported without risk factors. RESULTS: For all years, the numbers of HIV/AIDS and AIDS diagnoses were consistently higher among non-Hispanic blacks than among other races and ethnicities. In the 32 states with HIV reporting, the HIV/AIDS diagnosis rate in 2003 was 74 per 100,000 for blacks, 25 per 100,000 for Hispanics, 11 per 100,000 for American Indians/Alaska Natives, nine per 100,000 for whites, and seven per 100,000 for Asians/Pacific Islanders. The rates for persons living with HIV/AIDS at the end of 2003 were highest for blacks (765 per 100,000) and Hispanics (220 per 100,000). In the 50 states and the District of Columbia, AIDS diagnosis rates in 2003 were 58 per 100,000 for blacks, 20 per 100,000 for Hispanics, eight per 100,000 for American Indians/Alaska Natives, and four per 100,000 for Asians/Pacific Islanders. CONCLUSION: HIV/AIDS disproportionately affects minority races and ethnicities in the United States. To reduce rates of HIV/AIDS in these populations, effective and culturally appropriate prevention interventions must be developed and implemented.
PMCID: PMC2640648  PMID: 16080451
12.  Associations between Intimate Partner Violence and Health among Men Who Have Sex with Men: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001609.
Ana Maria Buller and colleagues review 19 studies and estimate the associations between the experience and perpetration of intimate partner violence and various health conditions and sexual risk behaviors among men who have sex with men.
Please see later in the article for the Editors' Summary
Background
Intimate partner violence (IPV) among men who have sex with men (MSM) is a significant problem. Little is known about the association between IPV and health for MSM. We aimed to estimate the association between experience and perpetration of IPV, and various health conditions and sexual risk behaviours among MSM.
Methods and Findings
We searched 13 electronic databases up to 23 October 2013 to identify research studies reporting the odds of health conditions or sexual risk behaviours for MSM experiencing or perpetrating IPV. Nineteen studies with 13,797 participants were included in the review. Random effects meta-analyses were performed to estimate pooled odds ratios (ORs). Exposure to IPV as a victim was associated with increased odds of substance use (OR = 1.88, 95% CIOR 1.59–2.22, I2 = 46.9%, 95% CII2 0%–78%), being HIV positive (OR = 1.46, 95% CIOR 1.26–1.69, I2 = 0.0%, 95% CII2 0%–62%), reporting depressive symptoms (OR = 1.52, 95% CIOR 1.24–1.86, I2 = 9.9%, 95% CII2 0%–91%), and engagement in unprotected anal sex (OR = 1.72, 95% CIOR 1.44–2.05, I2 = 0.0%, 95% CII2 0%–68%). Perpetration of IPV was associated with increased odds of substance use (OR = 1.99, 95% CIOR 1.33–2.99, I2 = 73.1%). These results should be interpreted with caution because of methodological weaknesses such as the lack of validated tools to measure IPV in this population and the diversity of recall periods and key outcomes in the identified studies.
Conclusions
MSM who are victims of IPV are more likely to engage in substance use, suffer from depressive symptoms, be HIV positive, and engage in unprotected anal sex. MSM who perpetrate IPV are more likely to engage in substance use. Our results highlight the need for research into effective interventions to prevent IPV in MSM, as well as the importance of providing health care professionals with training in how to address issues of IPV among MSM and the need to raise awareness of local and national support services.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Intimate partner violence (IPV, also called domestic violence) is a common and widespread problem. Globally, nearly a third of women are affected by IPV at some time in their life, but the prevalence of IPV (the proportion of the population affected by IPV) varies widely between countries. In central sub-Saharan Africa, for example, nearly two-thirds of women experience IPV during their lifetime, whereas in East Asia only one-sixth of women are affected. IPV is defined as physical, sexual, or emotional harm that is perpetrated on an individual by a current or former partner or spouse. Physical violence includes hitting, kicking, and other types of physical force; sexual violence means forcing a partner to take part in a sex act when the partner does not consent; and emotional abuse includes threatening a partner by, for example, stalking them or preventing them from seeing their family. The adverse effects of IPV for women include physical injury, depression and suicidal behaviour, and sexual and reproductive health problems such as HIV infection and unwanted pregnancies.
Why Was This Study Done?
IPV affects men as well as women. Men can be subjected to IPV either by a female partner or by a male partner in the case of men who have sex with men (MSM, a term that encompasses homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men). Recent reviews suggest that the prevalence of IPV in same-sex couples is as high as the prevalence of IPV for women in opposite-sex relationships: reported lifetime prevalences of IPV in homosexual male relationships range between 15.4% and 51%. Little is known, however, about the adverse health effects of IPV on MSM. It is important to understand how IPV affects the health of MSM so that appropriate services and interventions can be provided to support MSM who experience IPV. In this systematic review (a study that identifies all the research on a given topic using predefined criteria) and meta-analysis (a study that combines the results of several studies using statistical methods), the researchers investigate the associations between the experience and perpetration of IPV and various health conditions and sexual risk behaviours among MSM.
What Did the Researchers Do and Find?
The researchers identified 19 studies that investigated associations between IPV and various health conditions or sexual risk behaviours (for example, unprotected anal sex, a risk factor for HIV infection) among MSM. The associations were expressed as odds ratios (ORs); an OR represents the odds (chances) that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. The researchers estimated pooled ORs from the data in the individual studies using meta-analysis. The pooled lifetime prevalence of experiencing any IPV (which was measured in six studies) was 48%. Exposure to IPV as a victim was associated with an increased risk of substance (alcohol or drug) use (OR = 1.88, data from nine studies), reporting depressive symptoms (OR = 1.52, data from three studies), being HIV positive (OR = 1.46, data from ten studies), and engagement in unprotected sex (OR = 1.72, data from eight studies). Perpetration of IPV was associated with an increased risk of substance abuse (OR = 1.99, data from six studies).
What Do These Findings Mean?
These findings suggest that MSM frequently experience IPV and that exposure to IPV is associated with several adverse health conditions and sexual risk behaviours. There were insufficient data to estimate the lifetime prevalence of IPV perpetration among MSM, but these findings also reveal an association between IPV perpetration and substance use. The accuracy of these findings is limited by heterogeneity (variability) between the studies included in the meta-analyses, by the design of these studies, and by the small number of studies. Despite these and other limitations, these findings highlight the need to undertake research to identify interventions to prevent IPV among MSM and to learn more about the health effects of IPV among MSM. They highlight the importance of health care professionals being aware that IPV is a problem for MSM and of training these professionals to assess MSM for IPV. Finally, these results highlight the need to improve the availability and effectiveness of support services to which health care professionals can refer MSM experiencing or perpetrating IPV.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001609.
The World Health Organization provides detailed information on intimate partner violence
The US Centers for Disease Control and Prevention provides information about IPV and a fact sheet on understanding IPV that includes links to further resources
The UK National Health Service Choices website has a webpage about domestic violence, which includes descriptions of personal experiences
The US National Domestic Violence Hotline provides confidential help and support to people experiencing IPV, including MSM; its website includes personal stories of IPV
The US Gay Men's Domestic Violence Project/GLBTQ Domestic Violence Project provides support and services to MSM experiencing IPV; its website includes some personal stories
The UK not-for-profit organization Respect runs two advice lines: the Men's Advice Line provides advice and support for men experiencing domestic violence and abuse and the Respect Phoneline provides advice for domestic violence perpetrators and for professionals who would like further information about services for those using violence/abuse in their intimate partner relationships
The UK not-for-profit organization ManKind Initiative also provides support for male victims of IPV
The UK not-for-profit organization Broken Rainbow UK provides help and support for lesbians and MSM experiencing IPV
MedlinePlus provides links to other resources about domestic violence (in English and Spanish)
The UK charity Galop gives advice and support to people who have experienced biphobia, homophobia, transphobia, sexual violence, or domestic abuse
doi:10.1371/journal.pmed.1001609
PMCID: PMC3942318  PMID: 24594975
13.  Voluntary Medical Male Circumcision: A Framework Analysis of Policy and Program Implementation in Eastern and Southern Africa 
PLoS Medicine  2011;8(11):e1001133.
Kim Dickson and colleagues analyze the progress made by 13 priority countries toward scale-up of medical male circumcision programs, finding that the most successful programs involve country ownership of the program and have sustained leadership at all levels.
Background
Following confirmation of the effectiveness of voluntary medical male circumcision (VMMC) for HIV prevention, the World Health Organization and the Joint United Nations Programme on HIV/AIDS issued recommendations in 2007. Less than 5 y later, priority countries are at different stages of program scale-up. This paper analyzes the progress towards the scale-up of VMMC programs. It analyzes the adoption of VMMC as an additional HIV prevention strategy and explores the factors may have expedited or hindered the adoption of policies and initial program implementation in priority countries to date.
Methods and Findings
VMMCs performed in priority countries between 2008 and 2010 were recorded and used to classify countries into five adopter categories according to the Diffusion of Innovations framework. The main predictors of VMMC program adoption were determined and factors influencing subsequent scale-up explored. By the end of 2010, over 550,000 VMMCs had been performed, representing approximately 3% of the target coverage level in priority countries. The “early adopter” countries developed national VMMC policies and initiated VMMC program implementation soon after the release of the WHO recommendations. However, based on modeling using the Decision Makers' Program Planning Tool (DMPPT), only Kenya appears to be on track towards achievement of the DMPPT-estimated 80% coverage goal by 2015, having already achieved 61.5% of the DMPPT target. None of the other countries appear to be on track to achieve their targets. Potential predicators of early adoption of male circumcision programs include having a VMMC focal person, establishing a national policy, having an operational strategy, and the establishment of a pilot program.
Conclusions
Early adoption of VMMC policies did not necessarily result in rapid program scale-up. A key lesson is the importance of not only being ready to adopt a new intervention but also ensuring that factors critical to supporting and accelerating scale-up are incorporated into the program. The most successful program had country ownership and sustained leadership to translate research into a national policy and program.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than 2.5 million people (mostly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS and no HIV vaccine. Consequently, global efforts to combat HIV/AIDS are concentrating on evidence-based prevention strategies such as voluntary medical male circumcision (VMMC). Circumcision—the removal of the foreskin, a loose fold of skin that covers the head of the penis—reduced HIV transmission through sexual intercourse by 60% in men in trials undertaken in sub-Saharan Africa, so in 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended implementation of VMMC programs in countries with a generalized HIV epidemic and low levels of male circumcision. They also identified 13 countries in southern and eastern Africa as high priority countries for rapid VMMC scale-up. Mathematical modeling suggests that 20.3 million circumcisions by 2015 and 8.4 million circumcisions between 2016 and 2025 are needed to reach 80% VMMC coverage in these countries. If this coverage is achieved, it will avert about 3.4 million new HIV infections through 2025.
Why Was This Study Done?
Despite convincing evidence that VMMC is an effective, cost-saving intervention in the fight against HIV/AIDS, national VMMC scale-up programs in the priority countries are currently at very different stages. A better understanding of the challenges faced by these programs would help countries still in the early stages of VMMC scale-up implement their national programs and would facilitate implementation of other HIV prevention strategies. In this study, the researchers use the Diffusion of Innovations (DOI) theory to analyze progress towards VMMC scale-up in the priority countries and to identify the factors that may have expedited or hindered program scale-up. This theory seeks to explain how, why, and at what rate new ideas and technology spread through cultures. It posits that a few individuals (“innovators”) adopt new ideas before they become mainstream ideas. A few more individuals—the “early adopters”—follow the innovators. The “early majority” is the next group to adopt the innovation, followed by the “late majority” and the “laggards.”
What Did the Researchers Do and Find?
The researchers used the annual number of VMMCs performed in the priority countries since 2008 to classify the countries into DOI adopter categories. They calculated a total scale-up score for each country based on six key elements of program scale-up (such as whether and when a VMMC policy had been approved). Finally, they analyzed the association between the DOI adopter category and the scores for the individual scale-up elements to determine which elements predict adoption and VMMC scale-up. By the end of 2010, about 560,000 VMMCs had been completed, less than 3% of the target coverage for the priority countries. Kenya, the only DOI innovator country, had completed nearly two-thirds of the VMMCs needed to reach its target coverage and was the only country on track to reach its target. The early adopters (South Africa, Zambia, and Swaziland) had initiated VMMC program scale-up soon after the release of the 2007 recommendations and had started VMMC scale-up pilot programs in 2008 but were far from achieving their VMMC targets. Having a VMMC focal person, establishing a national policy, having an operational strategy, and establishing a pilot program all predicted early adoption of VMMC scale-up.
What Do These Findings Mean?
These findings show that, three years after the WHO/UNAIDS recommendation to integrate VMMC into comprehensive HIV prevention programs, VMMC scale-up activities had been initiated in all the priority countries but that progress towards the 80% coverage target was variable and generally poor. Importantly, they show that early adoption of VMMC as a national program had not necessarily resulted in rapid program scale-up. Although these findings may not be generalizable to other settings, they suggest that countries endeavoring to scale up VMMC (or other HIV prevention strategies) must not only be ready to adopt VMMC but must also ensure that all the factors critical to supporting and accelerating scale-up are incorporated into the scale-up program. Finally, these findings show that the most successful national programs are those that involve country ownership of the program and that have sustained leadership at all levels to facilitate the translation of research into national policies and programs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001133.
This study is part of a PLoS Collection of articles on VMMC (http://www.ploscollections.org/VMMC2011) and is further discussed in a PLoS Medicine Review Article by Hankins et al. (http://dx.doi.org/10.1371/journal.pmed.1001127)
Information is available from WHO, UNAIDS, and PEPFAR on all aspects of HIV/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 Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
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
Wikipedia has a page on Diffusion of Innovations theory (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
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.1001133
PMCID: PMC3226465  PMID: 22140368
14.  Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study 
PLoS Medicine  2010;7(1):e1000211.
Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda.
Background
There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.
Methods and Findings
A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.
Conclusions
The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 31 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 and no vaccine against HIV infection. Consequently, prevention of HIV transmission is extremely important. HIV is most often spread through unprotected sex with an infected partner. Individuals can reduce their risk of HIV infection, therefore, by abstaining from sex, by having one or a few sexual partners, and by always using a male or female condom. In addition, male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of penis—can halve HIV transmission rates to men resulting from sex with women. Thus, as part of its HIV prevention strategy, the World Health Organization (WHO) recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
One such country is Rwanda. Here, 3% of the adult population is infected with HIV but only 15% of men are circumcised—worldwide, about 30% of men are circumcised. Demand for circumcision is increasing in Rwanda but, before policy makers introduce a country-wide male circumcision program, they need to identify the most cost-effective way to increase circumcision rates. In particular, they need to decide the age at which circumcision should be offered. Circumcision soon after birth (neonatal circumcision) is quick and simple and rarely causes any complications. Circumcision of adolescents and adults is more complex and has a higher complication rate. Although several studies have investigated the cost-effectiveness (the balance between the clinical and financial costs of a medical intervention and its benefits) of circumcision in adult men, little is known about its cost-effectiveness in newborn boys. In this study, which is one of several studies on male circumcision being organized by the National AIDS Control Commission in Rwanda, the researchers model the cost-effectiveness of circumcision at different ages.
What Did the Researchers Do and Find?
The researchers developed a simple cost-effectiveness model and applied it to three hypothetical groups of Rwandans: newborn boys, adolescent boys, and adult men. For their model, the researchers calculated the effectiveness of male circumcision (the number of HIV infections averted) by estimating the reduction in the annual number of new HIV infections over time. They obtained estimates of the costs of circumcision (including the costs of consumables, staff time, and treatment of complications) from health care providers and adjusted these costs for the money saved through not needing to treat HIV in males in whom circumcision prevented infection. Using their model, the researchers estimate that each neonatal male circumcision would cost US$15 whereas each adolescent or adult male circumcision would cost US$59. Neonatal male circumcision, they report, would be cost-saving. That is, over a lifetime, neonatal male circumcision would save more money than it costs. Finally, using the WHO definition of cost-effectiveness (for a cost-effective intervention, the additional cost incurred to gain one year of life must be less than a country's per capita gross domestic product), the researchers estimate that, although adolescent circumcision would be highly cost-effective, circumcision of adult men would only be potentially cost-effective (but would likely prove cost-effective if the additional infections that would occur from men to their partners without a circumcision program were also taken into account).
What Do These Findings Mean?
As with all modeling studies, the accuracy of these findings depends on the many assumptions included in the model. However, the findings suggest that male circumcision for infants for the prevention of HIV infection later in life is highly cost-effective and likely to be cost-saving and that circumcision for adolescents is cost-effective. The researchers suggest, therefore, that policy makers in Rwanda and in countries with similar HIV infection and circumcision rates should scale up male circumcision programs across all age groups, with high priority being given to the very young. If infants are routinely circumcised, they suggest, circumcision of adolescent and adult males would become a “catch-up” campaign that would be needed at the start of the program but that would become superfluous over time. Such an approach would represent a switch from managing the HIV epidemic as an emergency towards focusing on sustainable, long-term solutions to this major public-health problem.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000211.
This study is further discussed in a PLoS Medicine Perspective by Seth Kalichman
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information is available from the Joint United Nations Programme on HIV/AIDS (UNAIDS) on HIV infection and AIDS and on male circumcision in relation to HIV 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 Africa, and on circumcision and HIV (some information in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
The National AIDS Control Commission of Rwanda provides detailed information about HIV/AIDS in Rwanda (in English and French)
doi:10.1371/journal.pmed.1000211
PMCID: PMC2808207  PMID: 20098721
15.  Cost-Effectiveness of Pooled Nucleic Acid Amplification Testing for Acute HIV Infection after Third-Generation HIV Antibody Screening and Rapid Testing in the United States: A Comparison of Three Public Health Settings 
PLoS Medicine  2010;7(9):e1000342.
Angela Hutchinson and colleagues conducted a cost-effectiveness analysis of pooled nucleic acid amplification testing following HIV testing and show that it is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Background
Detection of acute HIV infection (AHI) with pooled nucleic acid amplification testing (NAAT) following HIV testing is feasible. However, cost-effectiveness analyses to guide policy around AHI screening are lacking; particularly after more sensitive third-generation antibody screening and rapid testing.
Methods and Findings
We conducted a cost-effectiveness analysis of pooled NAAT screening that assessed the prevention benefits of identification and notification of persons with AHI and cases averted compared with repeat antibody testing at different intervals. Effectiveness data were derived from a Centers for Disease Control and Prevention AHI study conducted in three settings: municipal sexually transmitted disease (STD) clinics, a community clinic serving a population of men who have sex with men, and HIV counseling and testing sites. Our analysis included a micro-costing study of NAAT and a mathematical model of HIV transmission. Cost-effectiveness ratios are reported as costs per quality-adjusted life year (QALY) gained in US dollars from the societal perspective. Sensitivity analyses were conducted on key variables, including AHI positivity rates, antibody testing frequency, symptomatic detection of AHI, and costs. Pooled NAAT for AHI screening following annual antibody testing had cost-effectiveness ratios exceeding US$200,000 per QALY gained for the municipal STD clinics and HIV counseling and testing sites and was cost saving for the community clinic. Cost-effectiveness ratios increased substantially if the antibody testing interval decreased to every 6 months and decreased to cost-saving if the testing interval increased to every 5 years. NAAT was cost saving in the community clinic in all situations. Results were particularly sensitive to AHI screening yield.
Conclusions
Pooled NAAT screening for AHI following negative third-generation antibody or rapid tests is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since 1981, acquired immunodeficiency syndrome (AIDS) has killed about 25 million people and about 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV, which is most often transmitted through unprotected sex with an infected partner or injection drug use, infects and kills immune system cells, leaving infected individuals susceptible to other infectious diseases. The first, often undiagnosed stage of HIV infection—acute HIV infection (AHI)—lasts a few weeks and sometimes involves a flu-like illness. During AHI, the immune system responds to HIV by beginning to make antibodies that recognize the virus but seroconversion—the appearance of detectable amounts of antibody in the blood—takes 6–12 weeks. During the second, symptom-free stage of HIV infection, which can last many years, the virus gradually destroys the immune system so that by the third stage of infection unusual infections (for example, persistent yeast infections) begin to occur. The final stage of infection (AIDS) is characterized by multiple severe infections and by the development of unusual cancers.
Why Was This Study Done?
Antiretroviral drugs control HIV infections but don't cure them. It is very important, therefore, to prevent HIV transmission by avoiding HIV risk behaviors that increase the risk of HIV infection such as having sex without a condom or with many partners. Individuals with AHI in particular need to avoid high-risk behaviors because these people are extremely infectious. However, routine tests for HIV infection that measure antibodies in the blood often give false-negative results in people with AHI because of the time lag between infection and seroconversion. Nucleic acid amplification testing (NAAT), which detects HIV genetic material in the blood, is a more accurate way to diagnose AHI but is expensive. In this study, the researchers investigate whether pooled NAAT screening (specimens are pooled before testing to reduce costs) for AHI in clinic settings after third-generation antibody testing is a cost-effective HIV prevention strategy. That is, does the gain in quality-adjusted life years (QALY, a measure of the quantity and quality of life generated by healthcare interventions) achieved by averting new HIV infections outweigh the costs of pooled NAAT screening?
What Did the Researchers Do and Find?
The researchers combined effectiveness data from a US study in which AHI was detected using pooled NAAT in three settings (sexually transmitted disease [STD] clinics, a community clinic serving men who have sex with men [MSM], and HIV counseling/testing sites) with a “micro-costing” study of NAAT and a mathematical model of HIV transmission. They then calculated the costs per QALY gained (the cost-effectiveness ratio) as a result of HIV prevention by identification and notification of people with AHI through pooled NAAT screening compared with repeat antibody testing. Pooled NAAT for AHI screening following annual antibody testing (the recommended testing interval for high-risk individuals), they estimate, would cost US$372,300 and US$484,400 per QALY gained for the counseling/testing sites and STD clinics, respectively, whereas pooled NAAT for AHI screening was cost-saving for the community clinic serving MSM. The cost-effectiveness ratio increased for the counseling/testing sites and STD clinics when the antibody testing interval was decreased to 6 months but remained cost-saving for the community clinic. With an antibody testing interval of 5 years, pooled NAAT was cost-saving in all three settings.
What Do These Findings Mean?
Cost-effectiveness ratios of US$100,000–US$200,000 are considered acceptable in the US. These results suggest therefore, that the cost of pooled NAAT screening for AHI following negative third-generation antibody testing is not acceptable at the recommended testing interval for high-risk individuals except in settings where HIV infection is very common such as clinics serving MSM. The researchers reach a similar conclusion in a separate cost-effectiveness analysis of pooled NAAT screening following a negative rapid HIV test. Although the accuracy of these results depends on numerous assumptions made in the cost-effectiveness analyses (for example, the degree to which awareness of HIV status affects the behavior of people with AHI), sensitivity analyses (investigations of the effect of altering key assumptions) show that these findings are not greatly affected by changes in many of these assumptions. Thus, the researchers conclude, NAAT screening should be reserved for settings that serve populations in which there are very high levels of new 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.1000342.
The US Centers for Disease Control and Prevention provides information on HIV infection and AIDS and on HIV testing and diagnosis
HIV InSite has information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS nonprofit organization on many aspects of HIV/AIDS, including HIV testing (in English and Spanish)
MedlinePlus has links to further resources on AIDS (in English and Spanish)
The UK National Institute of Health and Clinical Excellence has a page on measuring effectiveness and cost-effectiveness
doi:10.1371/journal.pmed.1000342
PMCID: PMC2946951  PMID: 20927354
16.  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
17.  Racial/ethnic and sexual behavior disparities in rates of sexually transmitted infections, San Francisco, 1999-2008 
BMC Public Health  2010;10:315.
Background
Racial/ethnic minorities and men who have sex with men (MSM) represent populations with disparate sexually transmitted infection (STI) rates. While race-specific STI rates have been widely reported, STI rates among MSM is often challenging given the absence of MSM population estimates. We evaluated the race-specific rates of chlamydia and gonorrhea among MSM and non-MSM in San Francisco between 1999-2008.
Methods
2000 US Census data for San Francisco was used to estimate the number of African-American, Asian/Pacific Islander, Hispanic, and white males. Data from National HIV Behavioral Surveillance (NHBS) MSM 1, conducted in 2004, was used to estimate the total number of MSM in San Francisco and the size of race/ethnic sub-populations of MSM. Non-MSM estimates were calculated by subtracting the number of estimated MSM from the total number of males residing in San Francisco. Rates of MSM and non-MSM gonorrhea and chlamydia reported between 1999 and 2008 were stratified by race/ethnicity. Ratios of MSM and non-MSM rates of morbidity were calculated by race/ethnicity.
Results
Between 1999-2008, MSM accounted for 72% of gonorrhea cases and 51% of chlamydia cases. Throughout the study period, African-American MSM had the highest chlamydia rate with 606 cases per 100,000 in 1999 increasing to 2067 cases per 100,000 in 2008. Asian/Pacific Islander MSM consistently had the lowest rate among MSM with1003 cases per 100,000 in 2008. The ratio of MSM/non-MSM for chlamydia was highest among whites 11.6 (95% CI: 8.8-14.4) and Asian/Pacific Islanders 8.6 (95% CI: 6.2-11), and lowest among African-Americans 1.53 (95% CI: 1.2-1.9) and Hispanics 4.43 (95% CI: 2.8-6.0). Gonorrhea rates were similar for African-American, white, and Hispanic MSM between 2137-2441 cases per 100,000 in 2008. Asian/Pacific Islander MSM had the lowest gonorrhea rate with 865 cases per 100,000 in 2008. The ratio of MSM/non-MSM for gonorrhea was highest among whites 11.6 (95% CI: 8.8-14.4) and Asian/Pacific Islanders 8.6 (95% CI: 6.2-11), and lowest among African-Americans 1.53 (95% CI: 1.2-1.9) and Hispanics 4.43 (95% CI: 2.8-6.0).
Conclusions
For all racial/ethnic groups in San Francisco, MSM carried a substantially higher burden of STIs compared to non-MSM except among African-American men. These racial and sexual behavior disparities warrant further public health attention and resources.
doi:10.1186/1471-2458-10-315
PMCID: PMC2903517  PMID: 20525397
18.  Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America 
In a large North American cohort study, anal cancer incidence rates were substantially higher for HIV-infected men who have sex with men, other men, and women compared with HIV-uninfected individuals. Rates increased from 1996–1999 to 2000–2003 but plateaued by 2004–2007.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men).
Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007.
Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
doi:10.1093/cid/cir1012
PMCID: PMC3297645  PMID: 22291097
19.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501
20.  The Cost-Effectiveness of Preexposure Prophylaxis for HIV Prevention in Men Who Have Sex with Men in the United States 
Annals of internal medicine  2012;156(8):541-550.
Background
In a recent randomized controlled trial, daily oral preexposure chemoprophylaxis (PrEP) was shown to be effective for HIV prevention in men who have sex with men (MSM). The United States Centers for Disease Control and Prevention (CDC) recently provided interim guidance for PrEP use among MSM who are at high risk for acquiring HIV. Previous studies failed to reach a consistent estimate of its cost-effectiveness.
Objective
To estimate the effectiveness and cost-effectiveness of PrEP in MSM in the United States.
Design
Dynamic model of HIV transmission and progression combined with a detailed economic analysis.
Data Sources
Published literature.
Target Population
MSM aged 13–64 in the United States.
Time Horizon
Lifetime.
Perspective
Societal.
Interventions
We evaluated PrEP for the general MSM population and for high-risk MSM. We assumed that PrEP reduces infection risk by 44%, based on clinical trial results.
Outcome Measures
New HIV infections, discounted quality-adjusted life-years (QALYs) and costs, and incremental cost-effectiveness ratios.
Results of Base-Case Analysis
If PrEP is initiated in 20% of MSM in the United States, we estimate a 13% reduction in new HIV infections and a gain of 550,166 QALYs over 20 years at a cost of $172,091/QALY gained. Initiating PrEP in a larger proportion of MSM averts more infections but at increasing cost per QALY gained ($216,480/QALY gained when 100% of MSM receive PrEP). Using PrEP only in high-risk MSM can improve its cost-effectiveness. PrEP costs approximately $50,000/QALY gained for MSM with 5 annual partners on average. PrEP for all high-risk MSM for 20 years leads to $75 billion in healthcare-related costs incremental to the status quo and costs $600,000 per HIV infection averted, compared with incremental costs of $95 billion and $2 million per infection averted for 20% coverage of all MSM.
Results of Sensitivity Analysis
PrEP use in the general MSM population costs less than $100,000/QALY gained if the daily cost of antiretroviral drugs for PrEP is less than $15 or if PrEP efficacy is greater than 75%.
Limitation
When examining PrEP use in high-risk MSM, we did not model mixing between low- and high-risk MSM because of lack of data on mixing patterns.
Conclusion
Use of PrEP for HIV prevention in the general MSM population could prevent a substantial number of HIV infections but is expensive. PrEP use in high-risk MSM compares favorably to other interventions considered cost-effective, but could result in annual expenditures on PrEP of over $4 billion.
doi:10.1059/0003-4819-156-8-201204170-00001
PMCID: PMC3690921  PMID: 22508731
21.  Estimated HIV Incidence in the United States, 2006–2009 
PLoS ONE  2011;6(8):e17502.
Background
The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology.
Methodology
We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups.
Principal Findings
Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%.
Conclusions/Significance
Overall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence.
doi:10.1371/journal.pone.0017502
PMCID: PMC3149556  PMID: 21826193
22.  HIV, Gender, Race, Sexual Orientation, and Sex Work: A Qualitative Study of Intersectional Stigma Experienced by HIV-Positive Women in Ontario, Canada 
PLoS Medicine  2011;8(11):e1001124.
Mona Loutfy and colleagues used focus groups to examine experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada.
Background
HIV infection rates are increasing among marginalized women in Ontario, Canada. HIV-related stigma, a principal factor contributing to the global HIV epidemic, interacts with structural inequities such as racism, sexism, and homophobia. The study objective was to explore experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada.
Methods and Findings
We conducted a community-based qualitative investigation using focus groups to understand experiences of stigma and discrimination and coping methods among HIV-positive women from marginalized communities. We conducted 15 focus groups with HIV-positive women in five cities across Ontario, Canada. Data were analyzed using thematic analysis to enhance understanding of the lived experiences of diverse HIV-positive women. Focus group participants (n = 104; mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender) described stigma/discrimination and coping across micro (intra/interpersonal), meso (social/community), and macro (organizational/political) realms. Participants across focus groups attributed experiences of stigma and discrimination to: HIV-related stigma, sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work. Coping strategies included resilience (micro), social networks and support groups (meso), and challenging stigma (macro).
Conclusions
HIV-positive women described interdependent and mutually constitutive relationships between marginalized social identities and inequities such as HIV-related stigma, sexism, racism, and homo/transphobia. These overlapping, multilevel forms of stigma and discrimination are representative of an intersectional model of stigma and discrimination. The present findings also suggest that micro, meso, and macro level factors simultaneously present barriers to health and well being—as well as opportunities for coping—in HIV-positive women's lives. Understanding the deleterious effects of stigma and discrimination on HIV risk, mental health, and access to care among HIV-positive women can inform health care provision, stigma reduction interventions, and public health policy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
HIV-related stigma and discrimination—prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV—is a major factor contributing to the global HIV epidemic. HIV-related stigma, which devalues and stereotypes people living with HIV, increases vulnerability to HIV infection by reducing access to HIV prevention, testing, treatment, and support. At the personal (micro) level, HIV-related stigma can make it hard for people to take tests to determine their HIV status or to tell other people that they are HIV positive. At the social/community (meso) level, it can mean that HIV-positive people are ostracized from their communities. At the organizational/political (macro) level, it can mean that health-care workers treat HIV-positive people differently and that governments are deterred from taking fast, effective action against the HIV epidemic. In addition, HIV-related stigma is negatively associated with well-being among people living with HIV. Thus, among HIV-positive people, those who have experienced HIV-related stigma have higher levels of mental and physical illness.
Why Was This Study Done?
Racism (oppression and inequity founded on ethno-racial differences), sexism and gender discrimination (oppression and inequity based on gender bias in attitudes), and homophobia and transphobia (discrimination, fear, hostility, and violence towards nonheterosexual and transgender people, respectively) can also affect access to HIV services. However, little is known about how these different forms of stigma and discrimination interact (intersect). A better understanding of the effect of intersecting stigmas on people living with HIV could help in the development of stigma reduction interventions and HIV prevention, treatment and care programs, and could help to control global HIV infection rates. In this qualitative study (an analysis of people's attitudes and experiences rather than numerical data), the researchers investigate the intersection of HIV-related stigma, racism, sexism and gender discrimination, homophobia and transphobia among marginalized HIV-positive women in Ontario, Canada. As elsewhere in the world, HIV infection rates are increasing among women in Canada. Nearly 25% of people living with HIV in Canada are women and about a quarter of all new infections are in women. Moreover, there is a disproportionately high infection rate among marginalized women in Canada such as sex workers and lesbian, bisexual, and queer women.
What Did the Researchers Do and Find?
The researchers held 15 focus groups with 104 marginalized HIV-positive women who were recruited by word-of-mouth and through flyers circulated in community agencies serving women of diverse ethno-cultural origins. Each focus group explored topics that included challenges in daily life, medical issues and needs, and issues that were silenced within the participants' communities. The researchers analyzed the data from these focus groups using thematic analysis, an approach that identifies, analyzes, and reports themes in qualitative data. They found that women living with HIV in Ontario experienced multiple types of stigma at different levels. So, for example, women experienced HIV-related stigma at the micro (“If you're HIV-positive, you feel shameful”), meso (“The thing I hate most for people that test positive for HIV is that society ostracizes them”), and macro (“A lot of women are not getting employed because they have to disclose their status”) levels. The women also attributed their experiences of stigma and discrimination to sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work at all three levels and described coping strategies at the micro (resilience; “I always live with hope”), meso (participation in social networks), and macro (challenging stigma) levels.
What Do These Findings Mean?
These findings indicate that marginalized HIV-positive women living in Ontario experience overlapping forms of stigma and discrimination and that these forms of stigma operate over micro, meso, and macro levels, as do the coping strategies adopted by the women. Together, these results support an intersectional model of stigma and discrimination that should help to inform discussions about the complexity of stigma and coping strategies. However, because only a small sample of nonrandomly selected women was involved in this study, these findings need to be confirmed in other groups of HIV-positive women. If confirmed, the complex system of interplay of different forms of stigma revealed here should help to inform health-care provision, stigma reduction interventions, and public-health policy, and could, ultimately, help to bring the global HIV epidemic under control.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001124.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment; its publication HIV and stigma deals with HIV-related stigma in the UK
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on women, HIV, and AIDS, on HIV and AIDS stigma and discrimination, and on HIV/AIDS statistics for Canada (in English and Spanish)
The People Living with Stigma Index to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma; its website will soon include a selection of individual stories about HIV-related stigma
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001124
PMCID: PMC3222645  PMID: 22131907
23.  Bias in Online Recruitment and Retention of Racial and Ethnic Minority Men Who Have Sex With Men 
Background
The Internet has become an increasingly popular venue for men who have sex with men (MSM) to meet potential sex partners. Given this rapid increase in online sex-seeking among MSM, Internet-based interventions represent an important HIV (human immunodeficiency virus) prevention strategy. Unfortunately, black and Hispanic MSM, who are disproportionately impacted by the HIV epidemic in the United States, have been underrepresented in online research studies.
Objective
Our objective was to examine and quantify factors associated with underrecruitment and underretention of MSM of color in an online HIV behavioral risk research study of MSM recruited from an online social networking site.
Methods
Internet-using MSM were recruited through banner advertisements on MySpace.com targeted at men who reported in their MySpace profile their age as at least 18 and their sexual orientation as gay, bisexual, or unsure. Multivariable logistic regression models were used to estimate the odds stratified by race and ethnicity of the MySpace user clicking through the banner advertisement. To characterize survey retention, Kaplan-Meier survival curves and multivariable Cox proportional hazards models identified factors associated with survey dropout.
Results
Over 30,000 MySpace users clicked on the study banner advertisements (click-through rate of 0.37%, or 30,599 clicks from 8,257,271 impressions). Black (0.36% or 6474 clicks from 1,785,088 impressions) and Hispanic (0.35% or 8873 clicks from 2,510,434 impressions) MySpace users had a lower click-through rate compared with white (0.48% or 6995 clicks from 1,464,262 impressions) MySpace users. However, black men had increased odds of click-through for advertisements displaying a black model versus a white model (adjusted odds ratio [OR] = 1.83, 95% confidence interval [CI] 1.72 - 1.95), and Hispanic participants had increased odds of click-through when shown an advertisement displaying an Asian model versus a white model (adjusted OR = 1.70, 95% CI 1.62 - 1.79). Of the 9005 men who consented to participate, 6258 (69%) completed the entire survey. Among participants reporting only male sex partners, black non-Hispanic and Hispanic participants were significantly more likely to drop out of the survey relative to white non-Hispanic participants (hazard ratio [HR] = 1.6, 95% CI 1.4 - 1.8 and HR = 1.3, 95% CI 1.1 - 1.4, respectively). Men with a college-level of education were more likely to complete the survey than those with a high-school level of education (HR = 0.8, 95% CI 0.7 - 0.9), while men who self-identified as heterosexual were more likely to drop out of the survey compared with men who self-identified as gay (HR = 2.1, 95% CI 1.1 - 3.7).
Conclusions
This analysis identified several factors associated with recruitment and retention of MSM in an online survey. Differential click-through rates and increased survey dropout by MSM of color indicate that methods to recruit and retain black and Hispanic MSM in Internet-based research studies are paramount. Although targeting banner advertisements to MSM of color by changing the racial/ethnic composition of the advertisements may increase click-through, decreasing attrition of these study participants once they are engaged in the survey remains a challenge.
doi:10.2196/jmir.1797
PMCID: PMC3221372  PMID: 21571632
HIV infections/prevention and control; Internet; homosexuality male; research methodology; behavioral research
24.  Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding Male Circumcision for HIV Prevention in Eastern and Southern Africa 
PLoS Medicine  2011;8(11):e1001132.
Emmanuel Njeuhmeli and colleagues estimate the impact and cost of scaling up adult medical male circumcision in 13 priority countries in eastern and southern Africa, finding that reaching 80% coverage and maintaining it until 2025 would avert 3.36 million new HIV infections.
Background
There is strong evidence showing that voluntary medical male circumcision (VMMC) reduces HIV incidence in men. To inform the VMMC policies and goals of 13 priority countries in eastern and southern Africa, we estimate the impact and cost of scaling up adult VMMC using updated, country-specific data.
Methods and Findings
We use the Decision Makers' Program Planning Tool (DMPPT) to model the impact and cost of scaling up adult VMMC in Botswana, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zimbabwe, and Nyanza Province in Kenya. We use epidemiologic and demographic data from recent household surveys for each country. The cost of VMMC ranges from US$65.85 to US$95.15 per VMMC performed, based on a cost assessment of VMMC services aligned with the World Health Organization's considerations of models for optimizing volume and efficiencies. Results from the DMPPT models suggest that scaling up adult VMMC to reach 80% coverage in the 13 countries by 2015 would entail performing 20.34 million circumcisions between 2011 and 2015 and an additional 8.42 million between 2016 and 2025 (to maintain the 80% coverage). Such a scale-up would result in averting 3.36 million new HIV infections through 2025. In addition, while the model shows that this scale-up would cost a total of US$2 billion between 2011 and 2025, it would result in net savings (due to averted treatment and care costs) amounting to US$16.51 billion.
Conclusions
This study suggests that rapid scale-up of VMMC in eastern and southern Africa is warranted based on the likely impact on the region's HIV epidemics and net savings. Scaling up of safe VMMC in eastern and southern Africa will lead to a substantial reduction in HIV infections in the countries and lower health system costs through averted HIV care costs.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, about 2.5 million people (mainly 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 very important. Because the most common HIV transmission route is 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 partners, and by using male or female condoms. There is also strong evidence that voluntary medical male circumcision (VMMC)—the removal of the foreskin, the loose fold of skin that covers the head of the penis—reduces the heterosexual acquisition of HIV in men by about 60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered to men as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision. They also prioritized 13 countries in eastern and southern Africa for VMMC program scale-up.
Why Was This Study Done?
The impact of VMMC scale-up in terms of HIV infections and AIDS deaths averted (epidemiologic impact) is expected to be large, and the intervention should also reduce the costs associated with the treatment, care, and support of infected individuals. However, VMMC scale-up will require substantial funding and considerable effort by countries—many of which have weak health systems and limited resources—to train personnel, equip facilities, and provide the necessary commodities. To support planning for VMMC scale-up, the United States Agency for International Development Health Policy Initiative has collaborated with UNAIDS to develop the Decision Makers' Program Planning Tool (DMPPT), a mathematical model that allows analysts and decision makers to estimate the epidemiologic impact and cost of alternative VMMC scale-up programs. In this study, the researchers use DMPPT to estimate the impact and cost of scaling up adult VMMC in the 13 priority countries in eastern and southern Africa.
What Did the Researchers Do and Find?
The researchers derived VMMC unit costs for each priority country based on a cost assessment undertaken in Zimbabwe, one of the first countries to scale up VMMC services using WHO's “Models for Optimizing Volume and Efficiencies” (MOVE) guidelines. They fed these costs and recent epidemiologic data (including HIV infection rates and the effectiveness of VMMC in preventing HIV transmission) and demographic data (including the adult population size and pre-scale-up male circumcision prevalence) collected in each country into the DMPPT, together with information on the lifetime costs of HIV treatment. Results from running the DMPPT model suggest that scaling up adult VMMC to reach 80% coverage in the 13 priority countries by 2015 would require 20.33 million circumcisions to be completed between 2011 and 2015. To maintain this coverage, a further 8.42 million circumcisions would be required between 2016 and 2025. Such a scale-up would avert 3.36 million new HIV infections through 2025 and would cost US$2,000,000,000 between 2011 and 2025. However, it would result in net savings (because of averted treatment and care costs) of US$16,510,000,000.
What Do These Findings Mean?
These findings suggest that rapid VMMC scale-up in eastern and southern Africa is warranted, given its likely impact on the region's HIV epidemics and the resultant cost savings. However, the accuracy of these findings depends on the assumptions built into the DMPPT and on the data fed into it. For example, there could be risk behavior changes after circumcision. That is, risky sexual behaviors may increase in men who have been circumcised. However, the researchers show that, except in Rwanda, post-circumcision risk behavior change is unlikely to completely reverse the benefits of VMMC. These modeling results also assume that men seeking out VMMC services are typical of the general male population, but if they are actually at unusually low risk of HIV infection, then the benefits of VMMC reported here are likely to be overestimated. Finally, these findings assume 80% VMMC coverage. This may be optimistic, although results from Kenya indicate that this target is achievable. Thus, countries and their international partners must allocate sufficient resources to VMMC scale-up to achieve high coverage rates if they are to take full advantage of the benefits predicted here for VMMC scale-up.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001132.
This study is part of a PLoS Collection of articles on http://www.ploscollections.org/VMMC2011 and is further discussed in a PLoS Medicine Review Article by Hankins et al. (http://dx.doi.org/10.1371/journal.pmed.1001127)
Information is available from WHO, UNAIDS, and PEPFAR on all aspects of HIV/AIDS; the 2011WHO/UNAIDS progress report on VMMC scale-up in the 13 priority countries is available
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 Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
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, including information on the DMPPT and the MOVE guidance
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.1001132
PMCID: PMC3226464  PMID: 22140367
25.  HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis 
PLoS Medicine  2013;10(12):e1001568.
Erik Volz and colleagues use HIV genetic information from a cohort of men who have sex with men in Detroit, USA to dissect the timing of onward transmission during HIV infection.
Please see later in the article for the Editors' Summary
Background
Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. We conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM) and estimated incidence and transmission rates by stage of infection.
Methods and Findings
We analyzed 662 HIV-1 subtype B sequences collected between October 14, 2004, and February 24, 2012, from MSM in the Detroit metropolitan area, Michigan. These sequences were cross-referenced with a database of 30,200 patients diagnosed with HIV infection in the state of Michigan, which includes clinical information that is informative about the recency of infection at the time of diagnosis. These data were analyzed using recently developed population genetic methods that have enabled the estimation of transmission rates from the population-level genetic diversity of the virus. We found that genetic data are highly informative about HIV donors in ways that standard surveillance data are not. Genetic data are especially informative about the stage of infection of donors at the point of transmission. We estimate that 44.7% (95% CI, 42.2%–46.4%) of transmissions occur during the first year of infection.
Conclusions
In this study, almost half of transmissions occurred within the first year of HIV infection in MSM. Our conclusions may be sensitive to un-modeled intra-host evolutionary dynamics, un-modeled sexual risk behavior, and uncertainty in the stage of infected hosts at the time of sampling. The intensity of transmission during early infection may have significance for public health interventions based on early treatment of newly diagnosed individuals.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since the first recorded case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. About 34 million people are currently HIV-positive, and about 2.5 million people become newly infected with HIV every year. 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 only one or a few partners, and by always using condoms. Most people do not become ill immediately after infection with HIV, although some develop a short flu-like illness. The next stage of HIV infection, which may last more than ten years, also has no major symptoms, but during this stage, HIV slowly destroys immune system cells. Eventually, the immune system can no longer fight off infections by other disease-causing organisms, and HIV-positive people then develop one or more life-threatening AIDS-defining conditions, including unusual infections and specific types of cancer. HIV infection can be controlled, but not cured, by taking a daily cocktail of antiretroviral drugs.
Why Was This Study Done?
The design of effective programs to prevent the spread of HIV/AIDS depends on knowing how HIV transmissibility varies over the course of HIV infection. Consider, for example, a prevention strategy that focuses on increasing treatment rates: antiretroviral drugs, in addition to reducing illness and death among HIV-positive people, reduce HIV transmission from HIV-positive individuals. “Treatment as prevention” can only block transmissions that occur after diagnosis and entry into care. However, the transmissibility of HIV per sexual contact depends on a person's viral load, which peaks during early HIV infection, when people are often unaware of their HIV status and may still be following the high-risk patterns of sexual behavior that caused their own infection. Epidemiological surveillance data (information on HIV infections within populations) can be used to estimate how many new HIV infections occur within a population annually (HIV incidence) and the proportion of the population that is HIV-positive (HIV prevalence), but cannot be used to estimate the timing of transmission events. In this study, the researchers use “phylodynamic analysis” to estimate HIV incidence and prevalence and the timing of HIV transmission during infection. HIV, like many other viruses, rapidly accumulates genetic changes. The timing of transmission influences the pattern of these changes. Viral phylodynamic analysis—the quantitative study of how epidemiological, immunological, and evolutionary processes shape viral phylogenies (evolutionary trees)—can therefore provide estimates of transmission dynamics.
What Did the Researchers Do and Find?
The researchers obtained HIV sequence data (collected for routine surveillance of antiretroviral resistance mutations) and epidemiological surveillance data (including information on the stage of infection at diagnosis) for 662 HIV-positive men who have sex with men living in the Detroit metropolitan area of Michigan. They constructed a phylogenetic tree from the sequences using a “relaxed clock” approach and then fitted an epidemiological model (a mathematical model that represents the progress of individual patients through various stages of HIV infection) to the sequence data. Their approach, which integrates surveillance data and genetic data, yielded estimates of HIV incidence and prevalence among the study population similar to those obtained from surveillance data alone. However, it also provided information about HIV transmission that could not be obtained from surveillance data alone. In particular, it allowed the researchers to estimate that, in the current HIV epidemic among men who have sex with men in Detroit, 44.7% of HIV transmissions occur during the first year of infection.
What Do These Findings Mean?
The robustness of these findings depends on the validity of the assumptions included in the researchers' population genetic model and on the accuracy of the data fed into the model, and may not be generalizable to other cities or to other risk groups. Nevertheless, the findings of this analysis, which can be repeated in any setting where HIV sequence data for individual patients can be linked to patient-specific clinical and behavioral information, have important implications for HIV control strategies based on the early treatment of newly diagnosed individuals. Because relatively few infected individuals are diagnosed during early HIV infection, when the HIV transmission rate is high, it is unlikely, suggest the researchers, that the “treatment as prevention” strategy will effectively control the spread of HIV unless there are very high rates of HIV testing and treatment.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001568.
This study is further discussed in a PLOS Medicine Perspective by Timothy Hallett
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 treatment as prevention (in English and Spanish)
The PLOS Medicine Collection Investigating the Impact of Treatment on New HIV Infections provides more information about HIV treatment as prevention
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
The US National Institute of Health–funded HIV Sequence Database contains HIV sequences and tools to analyze these sequences
Patient stories about living with HIV/AIDS are available through Avert; the charity website Healthtalkonline also provides personal stories about living with HIV
doi:10.1371/journal.pmed.1001568
PMCID: PMC3858227  PMID: 24339751

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