Human papillomavirus clearance among males is associated with HIV acquisition and increased dendritic cell density in the foreskin.

BACKGROUND: The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated. METHODS: A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a(+) dendritic cells, CD4(+) T cells, and CD8(+) T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial. RESULTS: HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11-9.55] and 3.18 [95% CI, 1.14-8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a(+) dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm(2) [interquartile range {IQR}, 29.4-138.3 cells/mm(2)]), compared with males who were persistently negative for HPV (32.1 cells/mm(2) [IQR, 3.1-96.2 cells/mm(2)]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05). CONCLUSIONS: HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion.

The number of procedures required to achieve optimal competency with male circumcision: findings from a randomized trial in Rakai, Uganda.

OBJECTIVE: To assess the number of procedures required to achieve optimal competency (time required for surgery with minimal adverse events) in Rakai, Uganda, and thus facilitate the development of guidelines for training providers, as male circumcision reduces the acquisition of human immunodeficiency virus (HIV) in men and is recommended for HIV prevention. PATIENTS AND METHODS: In a randomized trial, 3011 men were circumcised, using the sleeve method, by six physicians who had completed training, which included 15-20 supervised procedures. The duration of surgery from local anaesthesia to wound closure, moderate or severe surgery-related adverse events (AEs), and wound healing were assessed in relation to the number of procedures done by each physician. RESULTS: The median age of the patients was 24 years. The number of procedures per surgeon was 20-981. The mean time required to complete surgery was approximately 40 min for the first 100 procedures and declined to 25 min for the subsequent 100 circumcisions. After controlling for the number of procedures there was no significant difference in duration of the surgery by patient HIV status or age. The rate of moderate and severe AEs was 8.8% (10/114) for the first 19 unsupervised procedures after training, 4.0% for the next 20-99 (13/328) and 2.0% for the last 100 (P for trend, 0.003). All AEs resolved with management. CONCLUSION: The completion of more than 100 circumcisions was required before newly trained physicians achieved the optimum duration of surgery. AEs were higher immediately after training and additional supervision is needed for at least the first 20 procedures after completing training.

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

BACKGROUND: The 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 FINDINGS: A 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). CONCLUSIONS: Overall, 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 #NCT00425984 and for HIV-positive men, #NCT000124878.

The effect of male circumcision on sexual satisfaction and function, results from a randomized trial of male circumcision for human immunodeficiency virus prevention, Rakai, Uganda.

OBJECTIVE: To investigate the relationship between adult male circumcision and sexual satisfaction and function in men, as observational studies on the effect of adult male circumcision on sexual satisfaction show conflicting results. SUBJECTS AND METHODS: We investigated self-reported sexual satisfaction and function among men enrolled in a randomized trial of male circumcision for human immunodeficiency virus (HIV) prevention conducted in Rakai, Uganda. In all, 4456 sexually experienced HIV-negative males aged 15-49 years were enrolled; 2210 were randomized to receive immediate circumcision (intervention arm) and 2246 to circumcision delayed for 24 months (control arm). Men were followed up at 6, 12 and 24 months, and information on sexual desire, satisfaction and erectile dysfunction was collected. These variables were compared between the study arms and over time within the study arms, using chi-square or Fisher's exact tests. The trial registration number is NCT00425984. RESULTS: There were no differences between the study arms at enrollment and problems with sexual satisfaction and function were reported by <2% of participants in both study arms at all time points. At 6 months, no difficulty with penetration was reported by 98.6% of circumcised men and 99.4% of controls (P = 0.02), and no pain on intercourse was reported by 99.4% circumcised and 98.8% of uncircumcised men (P = 0.05). There were no differences between the study arms in penetration or dyspareunia at later visits. Sexual satisfaction increased from 98.0% at enrollment to 99.9% at 2 years among the controls (P < 0.001), but there was no trend in satisfaction among circumcised men (enrollment 98.5%, 2 years 98.4%, P = 0.8). CONCLUSION: Adult male circumcision does not adversely affect sexual satisfaction or clinically significant function in men.