Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda.
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In Rakai, Uganda, human immunodeficiency virus (HIV)-positive men were randomized to undergo either immediate circumcision (intervention arm) or delayed circumcision (control arm). Penile swab samples were assayed for high-risk human papillomavirus (HR-HPV) by Roche HPV Linear Array at enrollment and at 24 months (intervention arm, 103 subjects; control arm, 107 subjects). Rate ratios (RRs) of HR-HPV were estimated by Poisson regression. At 24 months, HR-HPV prevalence was found in 57 (55.3%) of 103 subjects in the intervention arm and in 77 (71.7%) of 107 subjects in the control arm (RR, 0.77; 95% confidence interval [CI], 0.62-0.97). Multiple HR-HPV infections were found in 19 (22.4%) of 85 subjects in the intervention arm and in 45 (42.5%) of 106 subjects in the control arm (RR, 0.53; 95% CI, 0.33-0.83). New HR-HPV genotypes were acquired by 34 (42.0%) of 81 subjects in the intervention arm and by 53 (57.0%) 85 subjects in the control arm (RR, 0.74; 95% CI, 0.54-1.01; P = .06). Multiple new HR-HPV genotypes were acquired by 8 (9.9%) of 81 subjects in the intervention arm and by 23 (24.7%) of 93 subjects in the control arm (RR, 0.40; 95% CI, 0.19-0.84; P = .01). Circumcision did not affect the acquisition of single HR-HPV infections (RR, 1.00; 95% CI 0.65-1.53) or clearance of HR-HPV infections (RR, 1.09; 95% CI 0.94-1.27). Circumcision of HIV-positive men reduced the prevalence and incidence of multiple HR-HPV infections.Trial registration
ClinicalTrials.gov identifier: NCT00124878 .
SUBMITTER: Serwadda D
PROVIDER: S-EPMC2862639 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMale circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners.MethodsFemale partners of HIV-infected men (aged 15-49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878.Findings474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86-1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77-1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83-1·12; p=0·61).InterpretationBecause circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important.FundingBill & Melinda Gates Foundation and National Institutes of Health.
| S-EPMC3146628 | biostudies-literature
Project description:MethodsUncircumcised human immunodeficiency virus (HIV)-negative men aged 15-49 years were randomized to immediate circumcision (intervention arm, 441 subjects) or delayed circumcision (control arm, 399 subjects). Human papillomavirus (HPV) was detected by Roche HPV Linear Array at enrollment, and at 6, 12, and 24 months. Incident high-risk HPV (HR-HPV) was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RRs) and 95% confidence intervals (CIs) of HR-HPV acquisition were estimated by Poisson multiple regression.ResultsEnrollment characteristics were comparable between study groups. HR-HPV incidence was 19.7 cases per 100 person-years (PYs) in the intervention arm (70 cases per 355.8 PYs) and 29.4 cases per 100 PYs (125 cases per 424.8 PYs) in the control arm (RR, 0.67; 95% CI, 0.51-0.89; P = .006). The incidence of multiple HR-HPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28-0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17-1.64).ConclusionsMale circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men.Trial registrationClinicalTrials.gov identifier: NCT00425984 .
| S-EPMC2882881 | biostudies-literature
Project description: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 registrationhttp://www.ClinicalTrials.gov; for HIV-negative men #NCT00425984 and for HIV-positive men, #NCT000124878.
| S-EPMC2408615 | biostudies-literature
Project description:BackgroundRandomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men.MethodsIn two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878.FindingsDuring the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008).InterpretationOur findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important.FundingThe Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.
| S-EPMC3119044 | biostudies-literature
Project description:BackgroundObservational 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.Methods922 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.FindingsThe 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).InterpretationCircumcision 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.FundingBill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.
| S-EPMC2905212 | biostudies-literature
Project description:ObjectiveTo determine whether circumcision of HIV-positive men is associated with increased subsequent sexual risk behaviors which may place their female partners at risk.MethodsNewly circumcised and uncircumcised HIV-positive men in the Rakai Community Cohort Study were followed from baseline (July 2013-January 2015) to determine trend in sexual risk behaviors and association of circumcision with subsequent sexual risk behaviors at follow up (February 2015-September 2016). Risk behaviors included sexual activity, alcohol before sex, transactional sex, multiple sex partners, casual sex partners, and inconsistent condom use with casual partners. The association was evaluated using modified Poisson regression, and sensitivity analyses were performed after multiple imputation with chained equations for missing data.ResultsWe identified 538 eligible men, of whom 113(21.0%) were circumcised at baseline and 425(79.0%) were uncircumcised. Men in fishing communities were more likely to be circumcised (p = 0.032) as well as those exposed to targeted HIV messaging (p < 0.001). Overall, 188(34.9%) men were lost to follow up and most were uncircumcised (p = 0.020). Among those followed up, behaviors remained largely unchanged with no differences by circumcision status. Transactional sex appeared to be associated with circumcision in unadjusted analyses (PR = 1.58, 95%CI = 1.01,2.48; p = 0.045, p = 0.05) and adjusted analyses (adj.PR = 1.54, 95%CI = 1.06,2.23; p = 0.022). However, the association was no longer significant in sensitivity analyses after accounting for loss to follow up (adj.PR = 1.43, 95%CI = 0.98,2.08; p = 0.066). No association with circumcision was observed for other sexual risk behaviors.ConclusionWe found no association between circumcision of HIV-positive men and subsequent sexual risk behavior.
| S-EPMC6284241 | biostudies-literature
Project description:Male circumcision (MC) reduces high-risk human papillomavirus (HR-HPV) infection in female partners. We evaluated the intensity of HR-HPV viral DNA load in HIV-negative, HR-HPV-positive female partners of circumcised and uncircumcised men. HIV-negative men and their female partners were enrolled in randomized trials of MC in Rakai, Uganda. Vaginal swabs were tested for HR-HPV genotypes by Roche HPV Linear Array which provides a semi-quantitative measure of HPV DNA by the intensity of genotype-specific bands (graded:1-4). We assessed the effects of MC on female HR-HPV DNA load by comparing high intensity linear array bands (3-4) to low intensity bands (1-2) using an intention-to-treat analysis. Prevalence risk ratios (PRR) of high intensity bands in partners of intervention versus control arm men were estimated using log-binomial regression with robust variance. The trial included 335 women with male partners in the intervention arm and 340 in the control arm. At enrollment, the frequency of HR-HPV high intensity linear array bands was similar in both study arms. At 24 months follow-up, the prevalence of high intensity bands among women with detectable HR-HPV was significantly lower in partners of intervention arm (42.7%) than control arm men (55.1%, PRR?=?0.78, 95% CI 0.65-0.94, p?=?0.02), primarily among incident HR-HPV infections (PRR?=?0.66, 95% CI 0.50-0.87, p?=?0.003), but not persistent infections (PRR?=?1.02, 95% CI 0.83-1.24). Genotypes with high HR-HPV band intensity were more likely to persist (adjHR?=?1.27 95% CI 1.07-1.50), irrespective of male partner circumcision status. MC reduces HR-HPV DNA load in newly infected female partners.
| S-EPMC3732529 | biostudies-literature
Project description:Male circumcision reduces penile high-risk human papillomavirus (HR-HPV) prevalence in randomised trials. The goal of this study was to examine the effect of circumcision on HPV viral load among HPV-infected men in a randomised trial of male circumcision.In a randomised trial to assess the efficacy of circumcision on HIV acquisition in Rakai, Uganda, HIV-negative men were randomised to immediate (intervention) or delayed (control) circumcision and followed over 24 months. We performed quantitative-PCR HPV viral load assays on penile swabs which tested positive by Linear Array (LA) for six HR-HPV genotypes and estimated viral load in the remaining types by LA signal strength.At 24 months, circumcision intervention arm men infected with one of the six selected HR-HPV genotypes had a lower viral load and significantly reduced HR-HPV high LA band intensity (PRR=0.61, 95% CI 0.43 to 0.86) compared to infected men in the control arm of the trial. The decreased viral load associated with circumcision was seen among HPV infections acquired after enrolment but not among infections that persisted from trial enrolment to 24 months (p=0.80).The decreased penile HR-HPV shedding observed among HPV-infected circumcised men may help to explain the protective association observed between circumcision and reduced acquisition of HR-HPV in female partners.
| S-EPMC3706631 | biostudies-literature
Project description:Male circumcision (MC) reduces penile high-risk human papillomavirus (HR-HPV) on the coronal sulcus and urethra. HR-HPV varies by anatomic site, and it is unknown whether MC decreases HR-HPV on the penile shaft. We assessed the efficacy of MC to reduce HR-HPV on the penile shaft and compared it to known efficacy of MC to reduce HR-HPV on the coronal sulcus. HIV-negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR-HPV at 12 months postenrollment using the Roche HPV Linear Array assay. Among swabs with detectable ?-globin or HPV, year 1 HR-HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men [adjusted prevalence risk ratios (PRRs) = 0.57, 95% CI 0.39-0.84, p = 0.005]. On the shaft, year 1 HR-HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR = 0.66, 95% CI 0.39-1.12, p = 0.12). Efficacy of MC to reduce HR-HPV on the shaft was similar to efficacy on the coronal sulcus (p = 0.52). In a sensitivity analysis in which swabs without detectable ?-globin or HPV were included as HPV negative, prevalence of HR-HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%; PRR 0.57, 95% CI 0.33-0.99, p < 0.05). HR-HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs. 23.8%, respectively, p = 0.02) and circumcised men (21.5% vs. 15.5%, respectively, p = 0.24). MC reduced HR-HPV prevalence on both the coronal sulcus and shaft.
| S-EPMC3193547 | biostudies-literature
Project description:ObjectiveThe objective of the study was to assess effects of male circumcision on female genital symptoms and vaginal infections.Study designHuman immunodeficiency virus (HIV)-negative men enrolled in a trial were randomized to immediate or delayed circumcision (control arm). Genital symptoms, bacterial vaginosis (BV), and trichomonas were assessed in HIV-negative wives of married participants. Adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CIs) were assessed by multivariable log-binomial regression, intent-to-treat analyses.ResultsA total of 783 wives of control and 825 wives of intervention arm men were comparable at enrollment. BV at enrollment was higher in control (38.3%) than intervention arm spouses (30.5%, P = .001). At 1 year follow-up, intervention arm wives reported lower rates of genital ulceration (adjPRR, 0.78; 95% CI, 0.63-0.97), but there were no differences in vaginal discharge or dysuria. The risk of trichomonas was reduced in intervention arm wives (adjPRR, 0.52; 95% CI, 0.05-0.98), as were the risks of any BV (adjPRR, 0.60; 95% CI, 0.38-0.94) and severe BV (prevalence risk ratios, 0.39; 95% CI, 0.24-0.64).ConclusionMale circumcision reduces the risk of ulceration, trichomonas, and BV in female partners.
| S-EPMC2727852 | biostudies-literature