Background Observational studies suggest that male circumcision may provide protection against HIV-1 infection. A randomized, controlled intervention trial was conducted in a general population of South Africa to test this hypothesis. Methods and Findings A total of 3,274 uncircumcised men, aged 18–24 y, were randomized to a control or an intervention group with follow-up visits at months 3, 12, and 21. Male circumcision was offered to the intervention group immediately after randomization and to the control group at the end of the follow-up. The grouped censored data were analyzed in intention-to-treat, univariate and multivariate, analyses, using piecewise exponential, proportional hazards models. Rate ratios (RR) of HIV incidence were determined with 95% CI. Protection against HIV infection was calculated as 1 � RR. The trial was stopped at the interim analysis, and the mean (interquartile range) follow-up was 18.1 mo (13.0–21.0) when the data were analyzed. There were 20 HIV infections (incidence rate ¼0.85 per 100 person-years) in the intervention group and 49 (2.1 per 100 person-years) in the control group, corresponding to an RR of 0.40 (95% CI: 0.24%–0.68%; p , 0.001). This RR corresponds to a protection of 60% (95% CI: 32%–76%). When controlling for behavioural factors, including sexual behaviour that increased slightly in the intervention group, condom use, and health-seeking behaviour, the protection was of 61% (95% CI: 34%– 77%).

/pdf/randomized-controlled-intervention-trial-of-male-4r088cfjp6.pdf

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

http://www.medicine.mcgill.ca/epidemiology/hanley/c634/rates/CircumcisionHIV_Kenya.pdf

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

http://www.medicine.mcgill.ca/epidemiology/hanley/c634/rates/CircumcisionHIV_Uganda.pdf

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

Factors that increase transmission
 Factors that increase susceptibility
 STDs and HIV transmission
 STDs and community-based studies
 More than 42 million people worldwide are now infected with HIV, in spite of sustained prevention activities. Although the spread of HIV has been primarily sexual, epidemiological studies have indicated that the efficiency of the spread of HIV is poor, perhaps as infrequently as 1 in every 1,000 episodes of sexual intercourse. However, sexually transmitted diseases (STDs) that cause ulcers or inflammation greatly increase the efficiency of HIV transmission — by increasing both the infectiousness of, and the susceptibility to HIV infection. STDs might be particularly important in the early stages of a localized HIV epidemic, when people with risky sexual behaviour are most likely to become infected. In China, eastern Europe and Russia, there has been a remarkable increase in the incidence of STDs in recent years, and this is reflected in the rapid increase in the spread of HIV in these areas. Targeted STD detection and treatment should have a central role in HIV prevention in these emerging epidemics.

/pdf/the-role-of-sexually-transmitted-diseases-in-hiv-57d1p4kpqf.pdf

The role of sexually transmitted diseases in HIV transmission

Background The findings from observational studies reviews and meta- analyses supported by biological theories that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. Objectives 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse; 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis. Search strategy We searched online for published and unpublished studies in The Cochrane Library (issue 2 2002) MEDLINE (April 2002) EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts scanned reference lists of articles and contacted authors of included studies. Selection criteria We searched for randomized and quasi- randomized controlled trials of male circumcisions or in their absence observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. Data collection and analysis Independent reviewers selected studies assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. Main results We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 35 observational studies: 16 conducted in the general population and 19 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular important risk factors such as religion and sexual practices were not adequately accounted for in many of the included studies. General population study results: The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogeneous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High- risk group study results: The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross- sectional studies reporting unadjusted results found benefit from circumcision eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio ranging from 0.20 to 0.59 and all were significant. All three case- control studies found a protective effect of circumcision on HIV status two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects: No studies reported on the adverse effects of circumcision. In most studies circumcision had taken place during childhood or adolescence before the studies commenced. Authors conclusions We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV especially among high-risk groups. However observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV. (authors)

Male circumcision for prevention of heterosexual acquisition of HIV in men

Male circumcision is associated with reduced HIV acquisition. 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. 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 seroconversions occurred in 50 circumcised men whereas HIV acquisition was 16.7/100 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 of <50000 copies/ml (P = 0.02). 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. (authors)

Male circumcision and HIV acquisition and transmission: Cohort studies in Rakai, Uganda

Male circumcision and the risk of sexually transmitted infections and HIV in Rakai, Uganda.

Self-administered vaginal swabs for population-based assessment of Trichomonas vaginalis prevalence

Pregnancy was investigated among 4813 sexually active women aged 15-49 in rural Rakai District of southwestern Uganda who reported at least one sex partner during the previous year and provided a blood sample for HIV serology. 19.3% were pregnant with 83.7% of those pregnancies reported by the woman and 16.3% detected by urinary hCG. 953 (19.8%) women were infected with HIV-1. The prevalence of HIV infection varied by age from 7.3% among women aged 15-19 26.5% in the 20-29 age group 21.7% in women aged 30-39 and 9.7% in women aged 40-49. The prevalence of active syphilis was 9.3%. 21.4% of women infected with neither HIV nor syphilis were pregnant compared to 14.2% of HIV-negative women with active syphilis 8.5% of HIV-positive women with syphilis and 13.4% of HIV-positive women without syphilis. The age-specific pregnancy rates were lower in the HIV-infected than in the control women in all age groups. However among the HIV-negative women with active syphilis the reduction in pregnancy rates was mainly observed in the youngest age group 15-19. These younger women are likely to have relatively recent infections; early syphilis has a severe impact upon pregnancy loss. Among the 953 HIV-infected women 87.4% had no symptoms or signs suggestive of clinical HIV disease; 14.3% of these asymptomatic subjects were pregnant. Only 7.5% of 120 symptomatic HIV-infected women were pregnant. Pregnancy rates in the symptomatic HIV-positive women were 0% in 5 women with herpes zoster 5.9% in 34 women with chronic cough 6.5% in 31 women with oral candidiasis and 8.8% in 80 women who reported weight loss.

Reduced fertility in women with HIV infection; a population-based study in Uganda.

Human immunodeficiency virus type-1 infection associated with vaginal flora morphology and bacterial vaginosis (BV)

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