TY - JOUR
T1 - Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda
T2 - a randomised controlled trial
AU - Wawer, Maria J.
AU - Makumbi, Frederick
AU - Kigozi, Godfrey
AU - Serwadda, David
AU - Watya, Stephen
AU - Nalugoda, Fred
AU - Buwembo, Dennis
AU - Ssempijja, Victor
AU - Kiwanuka, Noah
AU - Moulton, Lawrence H.
AU - Sewankambo, Nelson K.
AU - Reynolds, Steven J.
AU - Quinn, Thomas C.
AU - Opendi, Pius
AU - Iga, Boaz
AU - Ridzon, Renee
AU - Laeyendecker, Oliver
AU - Gray, Ronald H.
N1 - Funding Information:
The trial was funded by the Bill & Melinda Gates Foundation as an investigator-initiated grant (number 22006). Additional support for laboratory analyses and training were provided, respectively, by the Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, and the Fogarty International Center (grants 5D43TW001508 and D43TW00015). The study was conducted by the Rakai Health Sciences Program, a research collaboration between the Uganda Virus Research Institute, and researchers at Makerere and Johns Hopkins Universities. We thank the members of the data and safety monitoring board, and the institutional review boards that provided oversight (the Committee for Human Research, Johns Hopkins Bloomberg School of Public Health, the Science and Ethics Committee of the Uganda Virus Research Institute, and the Western Institutional Review Board). We are also grateful for the advice provided by the Rakai community advisory board. We thank Edward Mbidde (Uganda Virus Research Institute) for his support. Finally, we wish to express our gratitude to the study participants whose commitment and cooperation made the study possible.
PY - 2009
Y1 - 2009
N2 - 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 μL 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. Findings: 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). Interpretation: 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. Funding: Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.
AB - 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 μL 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. Findings: 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). Interpretation: 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. Funding: Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.
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U2 - 10.1016/S0140-6736(09)60998-3
DO - 10.1016/S0140-6736(09)60998-3
M3 - Article
C2 - 19616720
AN - SCOPUS:67650429619
SN - 0140-6736
VL - 374
SP - 229
EP - 237
JO - The Lancet
JF - The Lancet
IS - 9685
ER -