The trial was also approved by the Scientific Commission of the French National Agency for AIDS Research (ANRS; protocol study no

The trial was also approved by the Scientific Commission of the French National Agency for AIDS Research (ANRS; protocol study no. circumcision on HIV acquisition appears independent of HSV-2 serostatus. strong class=”kwd-title” Keywords: Adolescent, Antibodies, Viral, blood, Circumcision, Male, HIV Infections, epidemiology, etiology, prevention & control, HIV-1, Herpes Genitalis, complications, epidemiology, immunology, Herpesvirus 2, PF-04620110 Human, immunology, Humans, Incidence, Longitudinal Studies, Male, Risk Factors, South Africa, epidemiology, Young Adult strong class=”kwd-title” Keywords: HSV-2, Male circumcision, Africa, Randomized controlled trial Introduction Genital herpes is a major public health problem worldwide [1]. Genital herpes is most frequently caused by the Herpes Simplex Virus type 2 (HSV-2). Clinical, biological and epidemiological studies support the hypothesis that HSV-2 increases the risk of HIV-1 acquisition 2- to 4-fold [2C10] and increases the risk of HIV-1 transmission [2, 11C14]. A recent meta analysis found that genital ulcer disease associated with HSV-2 significantly increased the odds of HIV-1 detection in genital shedding (OR, 2.4 [95% confidence interval CI, 1.2C4.9])[15]. HIV, in turn, increases the risk of HSV-2 transmission [2]. There is a direct relationship between CD4+ cell count and the rate of HSV-2 reactivation. Outbreaks of HSV- 2 are more severe, extensive, persistent, and invasive for those with advanced HIV disease [14, 16]. Persistent HSV-2 infection was one of the original opportunistic PF-04620110 infections that resulted in the identification of AIDS [17]. Three randomized controlled trials have demonstrated that male circumcision reduces the female-to-male sexual transmission of HIV by about 60% [18C20]. A meta-analysis of observational data EP showed that male circumcision reduces the risk of HSV-2 infection with a borderline statistical significance (summary RR, 0.88 [95% CI, 0.77C1.01]) [21]. The main objectives of this study were to estimate a) the effect of HSV-2 PF-04620110 status on HIV incidence among young males b) the population fraction of HIV infections attributable to HSV-2 infection and c) the effect of HSV-2 status on the protective effect of male circumcision on HIV acquisition by men. The secondary objective was to study the risk factors of HSV-2 incidence, especially the effect of male circumcision. For these analyses, we used data collected during a male circumcision randomized controlled trial conducted in Orange Farm (South Africa), which demonstrated a reducing effect of male circumcision on the acquisition of HIV [18]. Methods Collection of data The technical details of the trial (ANRS-1265), description of the participants and HIV testing methods having been published elsewhere [18], only a summary will be presented in this article. Between February 2002 and July 2004, 3274 uncircumcised males, aged 18 to 24, were recruited, randomized into two groups and followed-up. Recruitment was conducted independently of HIV and HSV-2 status. Male circumcision was offered to the intervention group immediately after randomization and to control group participants after the end of the follow-up period. During each follow-up visits at 3 (M3), 12 (M12) and 21 (M21) months, circumcision status was ascertained by a nurse by genital examination and a blood sample was obtained. In addition, information about sexual behavior was collected, including number of sexual partners as a function of time and history of condom use with each sexual partner. The dataset used in this study included 590 additional 21-month follow-up visits (20.0% of the total number of 21-month visits) which were not included when the analysis of the effect of male circumcision on HIV was published because corresponding biological data were not available at that time. Laboratory methods Plasma specimens were extracted from each blood sample immediately after collection, frozen at ?20C and kept frozen until processing. They were tested using an HSV type 2 specific IgG assay to detect HSV-2 antibodies with an index cutoff value of 1 1.1 (Kalon HSV-2 gG2 assay; Kalon Biologicals Ltd., Aldershot, UK), according to the manufacturers recommendations. Data analysis HIV status, treated as censored data with time being continuous, was established at each follow-up visit for periods of nonuniform duration. These data were modeled using a piecewise exponential proportional hazards model in which the baseline hazard was considered constant between consecutive follow-up visits. This theoretical model was established to take into account the precise duration between each visit as well as the time- dependent covariates. It was implemented by running a Poisson log-linear model on a dataset with each line corresponding to PF-04620110 one of three periods of follow-up: from randomization (M1) to M3,.