Elsevier

The Lancet

Volume 374, Issue 9685, 18–24 July 2009, Pages 229-237
The Lancet

Articles
Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(09)60998-3Get rights and content

Summary

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.

Introduction

Three trials of male circumcision in HIV-negative men, including one undertaken in Rakai, Uganda, showed that circumcision reduced male acquisition of HIV by 50–60%;1, 2, 3 as a result, male circumcision is now a recommended strategy for HIV prevention in men.4 As these prevention programmes are scaled up, it is inevitable that men who are infected with HIV will also request to be circumcised, partly to avoid stigmatisation. We previously reported that male circumcision was safe and reduced rates of genital ulcer disease in asymptomatic HIV-infected men with CD4-cell counts 350 cells per μL or more.5, 6 In view of the social considerations and clinical findings, WHO and UNAIDS have recommended that surgery should not be denied to HIV-infected men who request the procedure unless there are medical contraindications.4

A previous observational study in HIV-discordant couples in Rakai suggested a lower rate of male-to-female HIV transmission from circumcised HIV-infected men, particularly if their viral load was below 50 000 copies per mL.7 Two other observational studies also reported an association between male circumcision and reduced risk of HIV infection in female sexual partners.8, 9

In parallel to the trial of male circumcision in HIV-uninfected men in Rakai,3 we undertook a randomised controlled trial of male circumcision in HIV-infected men and enrolled their female partners. Trial objectives were to assess the safety of circumcision in HIV-infected men and the efficicacy of male circumcision for the prevention of sexually transmitted infections (STIs) in HIV-infected men (reported elsewhere),5, 6 and to test whether male circumcision would reduce transmission of HIV and STIs from HIV-infected men to their uninfected female sexual partners. Here, we report the trial results from female partners of HIV-infected men, including frequency of HIV and rates of STI symptoms and vaginal infections.

Section snippets

Participants

The trial was done in Rakai District, Uganda, between 2003 and 2007. Trial procedures for HIV-infected men, including consent, randomisation, and data and sample collection, were the same as those previously reported in the trial of male circumcision in HIV-uninfected men.3 In brief, men received an explanation of study goals and provided written informed consent for screening and HIV testing. Before screening and throughout the trial, men were offered HIV results, counselling, and information

Results

Figure 1 shows the trial profile. The modified ITT population for the analysis of male-to-female HIV transmission comprised 92 couples from the intervention group and 67 couples from the control group. An additional 29 HIV-uninfected female partners of men in the intervention group and 30 HIV-uninfected partners of men in the control group entered the study 6 months or more after their husband's enrolment. These women were excluded from the primary analysis because we did not know their HIV

Discussion

In this trial, circumcision of HIV-infected men did not reduce transmission of the virus to uninfected female partners. Furthermore, we cannot exclude the possibility of higher HIV transmission in couples who resumed intercourse before complete healing of the surgical wound. Since the duration of the study was limited and not all female partners completed 24 months of follow-up, we could not assess the long-term benefits or risks of male circumcision for HIV transmission to women. The findings

References (18)

  • RC Bailey et al.

    Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial

    Lancet

    (2007)
  • RH Gray et al.

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

    Lancet

    (2007)
  • B Auvert et al.

    Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial

    PLoS Med

    (2005)
  • New data on male circumcision and HIV prevention: policy and programme implications

  • G Kigozi et al.

    The safety of adult male circumcision in HIV-infected and uninfected men in Rakai, Uganda

    PLoS Med

    (2008)
  • Wawer MJ, Kigozi G, Serwadda D, et al. Trial of male circumcision in HIV+men and in women partners. 15th Conference on...
  • RH Gray et al.

    Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team

    AIDS

    (2000)
  • SH Kapiga et al.

    The incidence of HIV infection among women using family planning methods in Dar es Salaam, Tanzania

    AIDS

    (1998)
  • DJ Hunter et al.

    Sexual behavior, sexually transmitted diseases, male circumcision and risk of HIV infection among women in Nairobi, Kenya

    AIDS

    (1994)
There are more references available in the full text version of this article.

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