Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial

Abstract

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.).

Trial registration: ClinicalTrials.gov NCT00122525.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial Profile

This figure describes the state of the trial corresponding to planned visits up to 30 April 2005. HIV-positive and HIV-negative participants were randomized. All were followed, but only participants HIV-negative at randomization were analyzed and are represented in the three follow-up visits of the figure. After randomization, the participants could attend the 3-mo visit, miss it, or be excluded from follow-up (death or loss to follow-up). The non-excluded participants who attended the 3-mo visit could then attend the 12-mo visit, miss it, or be excluded (death or loss to follow-up). The non-excluded participants of the 12-mo visit could then attend the 21-mo visit, be excluded (death or loss to follow-up) or were planning to attend the 21-mo visit but had not yet done so, because of the interruption of the trial. *, did not come for the scheduled visit (refused, withdrew, moved away or died); **, no blood sample

Figure 2. Infection-Free Probability As a Function of Time and of Randomization

This figure represents the infection-free probability using a piecewise exponential distribution with boundaries at M3, M12, and M21 obtained with a Poisson log-linear model (see text). Each segment of exponential has been fitted to the data in each period for each randomization group. The 95% confidence intervals have been represented in the middle of each period. x/y is the number of HIV infections observed in each period (x) and the number of persons at the beginning of the period (y).