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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

Background Observational studies suggest that male circumcision may provide protection against HIV-1 infection. A randomized, controlled intervention trial was conducted in a general population of South Africa to test this hypothesis. Methods and Findings A total of 3,274 uncircumcised men, aged 18–24 y, were randomized to a control or an intervention group with follow-up visits at months 3, 12, and 21. Male circumcision was offered to the intervention group immediately after randomization and to the control group at the end of the follow-up. The grouped censored data were analyzed in intention-to-treat, univariate and multivariate, analyses, using piecewise exponential, proportional hazards models. Rate ratios (RR) of HIV incidence were determined with 95% CI. Protection against HIV infection was calculated as 1 − RR. The trial was stopped at the interim analysis, and the mean (interquartile range) follow-up was 18.1 mo (13.0–21.0) when the data were analyzed. There were 20 HIV infections (incidence rate = 0.85 per 100 person-years) in the intervention group and 49 (2.1 per 100 person-years) in the control group, corresponding to an RR of 0.40 (95% CI: 0.24%–0.68%; p < 0.001). This RR corresponds to a protection of 60% (95% CI: 32%–76%). When controlling for behavioural factors, including sexual behaviour that increased slightly in the intervention group, condom use, and health-seeking behaviour, the protection was of 61% (95% CI: 34%–77%). Conclusion Male circumcision provides a degree of protection against acquiring HIV infection, equivalent to what a vaccine of high efficacy would have achieved. Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa. (Preliminary and partial results were presented at the International AIDS Society 2005 Conference, on 26 July 2005, in Rio de Janeiro, Brazil.), The first trial of male circumcision for reducing the risk of HIV finds significantly lower new cases in the treatment group.

Bertrand Auvert and colleagues describe the large-scale roll-out of adult male circumcision through a program in South Africa., Background World Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting. Methods and Findings The ANRS 12126 “Bophelo Pele” project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project's main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing. Conclusion This study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa. Please see later in the article for the Editors' Summary, Editors' Summary Background Acquired immunodeficiency syndrome (AIDS) has killed about 25 million people since 1981, and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV infection is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having one or a few partners, and by always using a male or female condom. In addition, three trials in sub-Saharan Africa recently reported that medicalized adult male circumcision (AMC)—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce HIV transmission rates in men by more than a half. Thus, AMC delivered as a catch-up campaign—in the long-term, circumcision of male infants is likely to be a more sustainable strategy—has the potential to reduce the prevalence of HIV (the proportion of the population infected with HIV) in sub-Saharan Africa. Why Was This Study Done? The World Health Organization (WHO) and the Joint United Nations Programme on AIDS (UNAIDS) now recommend that AMC programs should be rolled-out wherever there is a generalized HIV epidemic and few men are circumcised. Accordingly, these organizations have defined a minimum package of AMC services and have issued guidelines and tools designed to engage communities in the roll-out and to ensure that appropriate AMC counseling and surgical facilities are available. But is rapid AMC roll-out feasible in real-life settings? Here, the researchers try to find out by studying the “Bophelo Pele” (Health First) project. This project, which follows the WHO/UNAIDS guidelines for AMC, aims to offer free, safe AMC services to all men aged 15 years or more living in the Orange Farm township in South Africa as part of a community-based intervention against HIV. Orange Farm is in a low-income region of South Africa where HIV prevalence is 15.2% and AMC prevalence is about 25%. What Did the Researchers Do and Find? Before the Bophelo Pele project started in January 2008, the researchers consulted the community about the implementation of AMC, helped to create a community advisory board, organized community workshops to discuss the project, and surveyed people's knowledge about AMC and willingness to undergo AMC. These activities indicated a high level of community support for the project and a high level of willingness among men to undergo AMC. Once the project started, the researchers used multiple communication channels to tell the Orange Farm residents about AMC and broader HIV prevention strategies and provided eligible men with counseling about AMC and with voluntary HIV counseling and testing during the recruitment process. Three days after recruitment, eligible men were circumcised free-of-charge at the project's main center, where three teams of one medical circumciser and five nurses were able to complete up to 150 AMCs per day. By November 2009, 14,011 men had been circumcised (more than a third of the eligible men in the township), and AMC uptake was still increasing steadily. Nearly all the men circumcised over one 2-month period rated the AMC services positively in a survey and adverse effects (all mild) occurred after fewer than 1 in 50 circumcisions. What Do These Findings Mean? These findings suggest that the rapid roll-out of high-quality, free AMC as an intervention against HIV has been successful in the Orange Farm township. However, other findings highlight some of the challenges that face AMC roll-out. For example, only a quarter of the participants agreed to voluntary HIV counseling and testing, which is worrying because newly circumcised HIV-positive men have an increased risk of transmitting HIV if they resume sexual activity too soon after the operation. Similarly, only two-thirds of the participants returned for a check-up after circumcision; this proportion needs to be increased to ensure the safety and efficacy of AMC programs. Nevertheless, these findings and those from similar intervention programs in Kenya and Uganda indicate that AMC scale-up should be feasible, at least in the short term, as an HIV prevention strategy in low-income communities where there is a high HIV prevalence and a low AMC rate. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000309. Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS HIV InSite has comprehensive information on all aspects of HIV/AIDS Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, and on circumcision and HIV (in English and Spanish) More information about male circumcision is available from WHO and from the Clearinghouse on Male Circumcision, including a June 2010 report from WHO/UNAIDS entitled Progress in male circumcision scale-up: country implementation and research update More information about the Bophelo Pele project is available