David Serwadda

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

BACKGROUND Male circumcision is associated with reduced HIV acquisition. METHODS HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. RESULTS The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50000 copies/ml (P = 0.02). INTERPRETATION Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.

Circumcision of HIV-Infected Men: Effects on High-Risk Human Papillomavirus Infections in a Randomized Trial in Rakai, Uganda

UNLABELLED 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 .

No difference in keratin thickness between inner and outer foreskins from elective male circumcisions in Rakai, Uganda.

It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more thinly keratinized inner foreskin. However, published data are contradictory and potentially confounded by medical indications for circumcision. We tested the hypothesis that the inner foreskin was more thinly keratinized than the outer foreskin using tissues from 19 healthy, HIV-uninfected men undergoing routine prophylactic circumcision in Rakai, Uganda. Sections from 3 foreskin anatomic sites (inner, outer, and frenar band) were snap-frozen separately. Two independent laboratories each separately stained, imaged, and measured keratin thicknesses in a blinded fashion. There was no significant difference in keratin thickness between the inner (mean = 14.67±7.48 µm) and outer (mean = 13.30±8.49 µm) foreskin, or between the inner foreskin and the frenar band (mean = 16.91±12.42 µm). While the frenar band showed the greatest intra-individual heterogeneity in keratin thickness, there was substantial inter-individual variation seen in all regions. Measurements made by the two laboratories showed high correlation (r = 0.741, 95% CI, 0.533–0.864). We conclude that, despite inter- and intra-individual variability, keratin thickness was similar in the inner and outer foreskin of healthy Ugandan men, and that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV acquisition.

Further experience with the world health organization clinical case definition for AIDS in Uganda

The diagnostic value of the World Health Organizations (WHOs) clinical case definition for acquired immunodeficiency syndrome (AIDS) was reassessed in 99 patients aged 16 years and above who presented to the Internal Medicine ward of Ugandas Mulago Hospital in August-December 1987. The 39 cases met the WHO clinical case definition of AIDS with at least 2 major and 1 minor signs; the control group was comprised of 60 consecutive admissions to the emergency ward who did not fulfill the WHO case definition. Blood samples from each study participant were tested for antibodies to human immunodeficiency virus (HIV)-1 through use of the Organon-Teknika enzyme-linked immunosorbent assay (ELISA) and the DuPont Western blot tests. 85% of the cases and 30% of controls were seropositive for HIV-1. Thus the WHO clinical case definition had a sensitivity of 65% a specificity of 88% and a positive predictive value for HIV-1 seropositivity of 85%. Similar values have been recorded in other centers in Uganda and in Zaire. Various modifications of the case definition were explored; however none resulted in any significant overall improvements in its diagnostic value. It was concluded that the WHO clinical case definition for AIDS is adequate in central African populations and its continued use is recommended.

Investigating Reproductive Tract Infections and other Gynaecological Disorders: Community interaction in studies of gynaecological morbidity: experiences in Egypt, India and Uganda

Reproductive tract infections and other gynaecological disorders among women represent an enormous global health burden. This significant new book will help focus research on an important though neglected area. The primary aims of the book are to provide an overview of reproductive tract infections and other gynaecological disorders, to highlight the conceptual and methodological challenges associated with undertaking research on this subject, and to serve as a reference for future research in this area. The book focuses on developing country settings, and recognises that gathering this sort of information requires a multidisciplinary and culturally sensitive approach. Findings from the research described in this book will undoubtedly assist physicians, social scientists, epidemiologists and public health practioners in evaluating the magnitude of this problem within the community at large and in identifying new potentially effective medical and behavioural interventions to address this problem.

Perceptions of Adolescent Pregnancy Among Teenage Girls in Rakai, Uganda:

The leading causes of death and disability among Ugandan female adolescents aged 15 to 19 years are pregnancy complications, unsafe abortions, and childbirth. Despite these statistics, our understanding of how girls perceive adolescent pregnancy is limited. This qualitative study explored the social and contextual factors shaping the perceptions of adolescent pregnancy and childbirth among a sample of 12 currently pregnant and 14 never pregnant girls living in the rural Rakai District of Uganda. Interviews were conducted to elicit perceived risk factors for pregnancy, associated community attitudes, and personal opinions on adolescent pregnancy. Findings indicate that notions of adolescent pregnancy are primarily influenced by perceptions of control over getting pregnant and readiness for childbearing. Premarital pregnancy was perceived as negative whereas postmarital pregnancy was regarded as positive. Greater understanding of the individual and contextual factors influencing perceptions can aid in development of salient, culturally appropriate policies and programs to mitigate unintended adolescent pregnancies.

Commentary: male circumcision for prevention of heterosexual acquisition of HIV in men: perspective from a trial team.

The Cochrane Collaboration (http://www.cochrane .org) is an international, non-profit organization that prepares and disseminates up-to-date systematic reviews on the effects of health-care interventions in order to help people make well-informed decisions. Systematic reviews aim to answer focused health-care questions by systematically identifying and evaluating all relevant research studies and synthesizing their results. In 2003, a Cochrane review of 35 observational studies investigating the effect of male circumcision on HIV acquisition in heterosexual men concluded that there was insufficient evidence of a protective effect against HIV. About that time, three randomized controlled trials (RCTs) to assess the efficacy of male circumcision for preventing HIV acquisition in men started recruiting in Africa. This review evaluates the results of these trials.