February 24, 2007
Male circumcision for HIV prevention in men in Rakai,
Uganda: a randomised trial
Ronald H Gray, Godfrey Kigozi, David Serwadda, Frederick Makumbi, Stephen Watya, Fred Nalugoda, Noah Kiwanuka, Lawrence H Moulton,
Mohammad A Chaudhary, Michael Z Chen, Nelson K Sewankambo, Fred Wabwire-Mangen, Melanie C Bacon, Carolyn F M Williams, Pius Opendi,
Steven J Reynolds, Oliver Laeyendecker, Thomas C Quinn, Maria J Wawer
Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition
in men. Our aim was to investigate the eF
ect of male circumcision on HIV incidence in men.
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 modi±
ed intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number
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
ed 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 eﬃ
cacy of intervention 51%,
95% CI 16–72; p=0·006). The as-treated eﬃ
cacy was 55% (95% CI 22–75; p=0·002); eﬃ
cacy 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.
Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision
can be recommended for HIV prevention in men.
A number of ecological and observational studies,
mainly from sub-Saharan Africa, have suggested that
male circumcision reduces the risk of HIV infection in
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).