Elsevier

The Lancet

Volume 369, Issue 9562, 24 February–2 March 2007, Pages 657-666
The Lancet

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Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial

https://doi.org/10.1016/S0140-6736(07)60313-4Get rights and content

Summary

Background

Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men.

Methods

4996 uncircumcised, HIV-negative men aged 15–49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984.

Findings

Baseline characteristics of the men in the intervention and control groups were much the same at enrolment. Retention rates were much the same in the two groups, with 90–92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0·66 cases per 100 person-years in the intervention group and 1·33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16–72; p=0·006). The as-treated efficacy was 55% (95% CI 22–75; p=0·002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30–77; p=0·003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3·6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up.

Interpretation

Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men.

Introduction

A number of ecological and observational studies, mainly from sub-Saharan Africa, have suggested that male circumcision reduces the risk of HIV infection in men.1, 2, 3, 4, 5 A meta-analysis of cross-sectional and prospective studies estimated that the adjusted summary rate ratio of male HIV acquisition associated with circumcision in general populations was 0·56 (95% CI 0·44–0·70); in high-risk populations the adjusted summary rate ratio was 0·29 (0·20–0·41).1 However, observational findings do not consistently show protective associations in all studies, and to exclude the possibility of confounding due to differences in sexual risk behaviours and cultural or religious practices associated with circumcision is difficult. Thus, the potential efficacy of circumcision for HIV prevention can be determined only by randomised trials. One randomised trial done in South Africa was ended early after an interim analysis showed that circumcision reduced HIV incidence by 60% (32–76).6 Two other randomised trials, one in Kisumu, Kenya and the other in Rakai, Uganda—the results of which we report here—were also stopped early on December 12, 2006, after interim analyses showed significant efficacy.

Section snippets

Patients

Our aim was to enrol 5000 HIV-negative, uncircumcised men aged 15–49 years who agreed to receive their HIV results through voluntary counselling and HIV testing provided by the study, and who consented to be randomly assigned to receive circumcision within about 2 weeks of enrolment (intervention group), or to have circumcision delayed for 24 months (control group). Screening and enrolment was done in a central study facility and in mobile facilities in the rural communities. Before screening,

Results

Figure 1 shows the trial profile. 5000 eligible men were initially enrolled. However, during follow-up we discovered that four men (two in each study group) had re-enrolled under assumed names. For these individuals, the first enrolment record was retained in the dataset for the primary intent-to-treat analysis and the second enrolment was deleted, leaving 4996 enrolled participants. 146 (6%) participants in the intervention group did not come for surgery within 6 months of randomisation and

Discussion

This large, randomised trial of adult male circumcision in a rural Ugandan population shows that such a surgical intervention reduces the risk of the acquisition of HIV in men. We noted a significant reduction in HIV incidence among circumcised men compared with uncircumcised control participants. The efficacy of circumcision for prevention of incident HIV was 51% in the Poisson intention-to-treat analysis; adjustment for enrolment characteristics, behaviours, and symptoms of sexually

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