Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial

Abstract

BackgroundObservational 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 FindingsA 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%).ConclusionMale 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.)

Male Circumcision and HIV Prevention: Is There Really Enough of the Right Kind of Evidence?

“…The trials in question were being undertaken following findings from observational studies that noted in some places (but not everywhere) an association between higher rates of male circumcision and lower HIV prevalence, [3][4][5][6] from systematic reviews of the literature on circumcision, 7,8 and from an earlier trial in Orange Farm in South Africa that found a partially protective effect of 61%. 9 Preliminary findings from the subsequent trials in Uganda and Kenya were reported after they were stopped early by their respective Data Safety and Monitoring Boards in December 2006, as these trials were reporting interim efficacy findings of 48% (Uganda) and 53% (Kenya), and it would have been unethical to continue.…”

Implementing voluntary medical male circumcision using an innovative, integrated, health systems approach: experiences from 21 districts in Zimbabwe

“…As voluntary medical male circumcision (VMMC) safely [1–13] reduces male HIV acquisition by up to 60% [14–16], the World Health Organization (WHO) set a target of 80% VMMC coverage in 14 priority countries with high HIV burdens [17]. By the end of 2016, 14.5 million VMMCs were completed [18].…”

Coming of age? Women’s sexual and reproductive health after twentyone years of democracy in South Africa

“…49 This is comparable to the protective effects of medical male circumcision against female-to-male HIV transmission in heterosexual men. 50 Insufficient detection power of Dapivirine's protective effects in women < 21 years, at greatest risk for HIV infection, was due to its inconsistent use. 49 An HIV vaccine as another biomedical strategy for primary prevention of HIV holds promise to curb HIV incidence, but it is unlikely to be realised for a further decade.…”