title: Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial.
abstract: 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.
authors.affiliation: Department of Population, Family and Reproductive Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA. mwawer@jhsph.edu
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Frederick
authors.initials: F
authors.lastname: Makumbi
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Stephen
authors.initials: S
authors.lastname: Watya
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.forename: Dennis
authors.initials: D
authors.lastname: Buwembo
authors.forename: Victor
authors.initials: V
authors.lastname: Ssempijja
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.forename: Nelson K
authors.initials: NK
authors.lastname: Sewankambo
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Pius
authors.initials: P
authors.lastname: Opendi
authors.forename: Boaz
authors.initials: B
authors.lastname: Iga
authors.forename: Renee
authors.initials: R
authors.lastname: Ridzon
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
mesh_terms: 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