Date Published: June 3, 2008
Publisher: Public Library of Science
Author(s): Godfrey Kigozi, Ronald H Gray, Maria J Wawer, David Serwadda, Frederick Makumbi, Stephen Watya, Fred Nalugoda, Noah Kiwanuka, Lawrence H Moulton, Michael Z Chen, Nelson K Sewankambo, Fred Wabwire-Mangen, Melanie C Bacon, Renee Ridzon, Pius Opendi, Victor Sempijja, Absolom Settuba, Denis Buwembo, Valerian Kiggundu, Margaret Anyokorit, James Nkale, Nehemia Kighoma, Blake Charvat, Patrick Sullivan
Abstract: BackgroundThe objective of the study was to compare rates of adverse events (AEs) related to male circumcision (MC) in HIV-positive and HIV-negative men in order to provide guidance for MC programs that may provide services to HIV-infected and uninfected men.Methods and FindingsA total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO] stage I or II and CD4 counts > 350 cells/mm3) were circumcised in two separate but procedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in rural Rakai, Uganda. Participants were followed at 1–2 d and 5–9 d, and at 4–6 wk, to assess surgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing were compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were estimated by multiple logistic regression, adjusting for baseline characteristics and postoperative resumption of sex. At enrollment, HIV-positive men were older, more likely to be married, reported more sexual partners, less condom use, and higher rates of sexually transmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were 3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91, 95% confidence interval [CI] 0.47–1.74). Infections were the most common AEs (2.6/100 in HIV-positive versus 3.0/100 in HIV-negative men). Risks of other complications were similar in the two groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIV-positive men and 95.8% in HIV-negative men (p = 0.007). AEs were more common in men who resumed intercourse before wound healing compared to those who waited (AdjOR 1.56, 95% CI 1.05–2.33).ConclusionsOverall, the safety of MC was comparable in asymptomatic HIV-positive and HIV-negative men, although healing was somewhat slower among the HIV infected. All men should be strongly counseled to refrain from intercourse until full wound healing is achieved.Trial registration:http://www.ClinicalTrials.gov; for HIV-negative men, #NCT00047073 and for HIV-positive men, #NCT00047073.
Partial Text: Three randomized trials have shown that male circumcision (MC) reduces the risk of male HIV acquisition in men by 50%–60% [1–3]. This finding suggests that the procedure may be an important means of HIV prevention in areas where circumcision is uncommon and where most HIV transmission is due to heterosexual intercourse. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) has now recommended that MC be promoted as an additional important strategy for preventing heterosexual HIV infection in men . The safety of surgery is a paramount consideration in planning future circumcision programs, both to minimize surgical risks and to provide guidelines for best practices in surgical procedures and postoperative care. Although information is available on postoperative complications in children and in HIV-negative men [1–3,5–8], there is little information on the safety of circumcision in HIV-infected men ; this presents an important programmatic issue since future circumcision services are likely to attract both HIV-infected and -uninfected men. Moreover, WHO/UNAIDS guidelines recommend that circumcision be provided to HIV-positive men if medically indicated or if they request the procedure. If surgery were to be unsafe in HIV-positive men, these individuals might have to either be excluded from adult MC programs, which would be potentially stigmatizing, or they might require specialized services for postoperative care, which could add to program costs and complexity.
The Rakai trials enrolled uncircumcised men aged 15–49 y who provided informed consent for screening and for randomization to immediate circumcision (the intervention arm), or circumcision delayed for 24 m (the control arm). The profile of the two parallel trials is provided in Figure 1, and details of trial design are reported elsewhere [1,9] and described in Texts S1 and S2. In brief, 6,461 consenting men were screened. If they were HIV-negative, had no contraindications against or medical indications for surgery, and accepted voluntary counseling and testing (VCT), they were enrolled into an NIH-funded trial of HIV-negative men. Men who were HIV-infected at screening, who did not have symptoms of AIDS (WHO stages I or II) or CD4 count < 350 cells/mm3, and who did not have contraindications to or indications for MC, were offered VCT and were enrolled into a Gates Foundation-funded trial. There were 540 screened men who were ineligible for either trial or who failed to complete enrollment and were excluded. The trials were conducted in 50 rural communities of southwestern Uganda, thus enrollment and follow-up were decentralized, but all surgery took place in fully equipped outpatient theaters located in a central facility. Table 1 shows the characteristics of the circumcised HIV-negative and HIV-positive men enrolled in the two trials. The differences in baseline distributions of all these characteristics were statistically significant. The HIV-positive men were substantially older than the HIV-negative men (median ages 32 versus 23 y, respectively), more likely to be married or divorced/separated, and less likely to have secondary or higher education. The HIV-infected men reported having more sexual partners and being less likely to consistently use condoms than the HIV-negative men. Moreover, the HIV-infected men reported higher levels of genital ulceration, urethral discharge, and dysuria. We found that the risks of moderate or severe AEs following adult MC were 3.1% in HIV-infected and 3.5% in HIV-negative men. Thus, we conclude that circumcision performed by adequately trained and equipped medical personnel is likely to be safe in HIV-infected men with WHO stage I or II disease and with a CD4 count > 350 cells/mm3. Completed wound healing was more rapid in the HIV-negative than in the HIV-positive men, but over 90% of wounds were certified as completely healed by 6 wk postoperatively. Resumption of intercourse before wound healing was associated with higher rates of surgical complications; thus both circumcised men and their partners should be strongly counseled to delay intercourse until full wound healing is achieved.