Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial.
BACKGROUND
Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners.


METHODS
922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4-cell counts 350 cells per microL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878.


RESULTS
The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0.36). Cumulative probabilities of female HIV infection at 24 months were 21.7% (95% CI 12.7-33.4) in the intervention group and 13.4% (6.7-25.8) in the control group (adjusted hazard ratio 1.49, 95% CI 0.62-3.57; p=0.368).


CONCLUSIONS
Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention.


BACKGROUND
Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.
Wawer
Maria J
MJ
Department of Population, Family and Reproductive Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA. mwawer@jhsph.edu
Makumbi
Frederick
F
Kigozi
Godfrey
G
Serwadda
David
D
Watya
Stephen
S
Nalugoda
Fred
F
Buwembo
Dennis
D
Ssempijja
Victor
V
Kiwanuka
Noah
N
Moulton
Lawrence H
LH
Sewankambo
Nelson K
NK
Reynolds
Steven J
SJ
Quinn
Thomas C
TC
Opendi
Pius
P
Iga
Boaz
B
Ridzon
Renee
R
Laeyendecker
Oliver
O
Gray
Ronald H
RH
D000293:Adolescent; D000328:Adult; D001294:Attitude to Health / Q000208:ethnology; D002944:Circumcision, Male / Q000009:adverse effects* / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000208:ethnology / Q000517:prevention & control* / Q000635:transmission*; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010353:Patient Education as Topic; D016016:Proportional Hazards Models; D040242:Risk Reduction Behavior; D012736:Sex Education; D012747:Sexual Partners / Q000523:psychology; D013240:Stereotyping; D016019:Survival Analysis; D013997:Time Factors; D014454:Uganda / Q000453:epidemiology; D016387:Women's Health / Q000208:ethnology; D014945:Wound Healing; D055815:Young Adult