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Background: Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation., Methods: In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression., Results: From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02)., Conclusions: Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

Objective: To test the hypothesis that increasing community antiretroviral therapy (ART) coverage would be associated with lower HIV incidence in female sex workers (FSWs) in Mombasa District, Kenya., Design: Prospective cohort study., Methods: From 1998 to 2012, HIV-negative FSWs were asked to return monthly for an interview regarding risk behavior and testing for sexually transmitted infections including HIV. We evaluated the association between community ART coverage and FSW's risk of becoming HIV infected using Cox proportional hazards models adjusted for potential confounding factors., Results: One thousand, four hundred and four FSWs contributed 4335 woman-years of follow-up, with 145 acquiring HIV infection (incidence 3.35/100 woman-years). The ART rollout began in 2003. By 2012, an estimated 52% of HIV-positive individuals were receiving treatment. Community ART coverage was inversely associated with HIV incidence (adjusted hazard ratio 0.77; 95% confidence interval 0.61-0.98; P = 0.03), suggesting that each 10% increase in coverage was associated with a 23% reduction in FSWs' risk of HIV acquisition. Community ART coverage had no impact on herpes simplex virus type-2 incidence (adjusted hazard ratio 0.97; 95% confidence interval 0.79-1.20; P = 0.8)., Conclusion: Increasing general population ART coverage was associated with lower HIV incidence in FSWs. The association with HIV incidence, but not herpes simplex virus type-2 incidence, suggests that the effect of community ART coverage may be specific to HIV. Interventions such as preexposure prophylaxis and antiretroviral-containing microbicides have produced disappointing results in HIV prevention trials with FSWs. These results suggest that FSWs' risk of acquiring HIV infection might be reduced through the indirect approach of increasing ART coverage in the community.

: Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. Antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breast-feeding transmission pairs, were compared. The envelope-binding titers were strongly correlated (r = 0.91, P < 0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, P < 0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and nontransmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.

HIV superinfection (reinfection) has been reported in several settings, but no study has been designed and powered to rigorously compare its incidence to that of initial infection. Determining whether HIV infection reduces the risk of superinfection is critical to understanding whether an immune response to natural HIV infection is protective. This study compares the incidence of initial infection and superinfection in a prospective seroincident cohort of high-risk women in Mombasa, Kenya. A next-generation sequencing-based pipeline was developed to screen 129 women for superinfection. Longitudinal plasma samples at <6 months, >2 years and one intervening time after initial HIV infection were analyzed. Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint. Phylogenetic evidence of polyphyly, confirmed by pairwise distance analysis, defined superinfection. Superinfection timing was determined by sequencing virus from intervening timepoints. These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened. Twenty-one cases of superinfection were identified for an estimated incidence rate of 2.61 per 100 person-years (pys). The incidence rate of initial infection among 1910 women in the same cohort was 5.75 per 100 pys. Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort. Superinfection incidence was significantly lower than initial infection incidence, with a hazard ratio of 0.47 (CI 0.29-0.75, p = 0.0019). This lower incidence of superinfection was only observed >6 months after initial infection. This is the first adequately powered study to report that HIV infection reduces the risk of reinfection, raising the possibility that immune responses to natural infection are partially protective. The observation that superinfection risk changes with time implies a window of protection that coincides with the maturation of HIV-specific immunity.

Background: Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART., Methods: In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression., Results: In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4-4.5), 11 (6.9%; 95% CI 3.1-10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1-5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression., Conclusion: The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.

Background: Our goal in the present study was to investigate the prevalence and correlates of genital warts in a population of female sex workers in Mombasa, Kenya. Because of the high prevalence of human immunodeficiency virus type 1 (HIV-1) in this population, we were particularly interested in the association between HIV-1 infection and genital warts., Methods: We conducted a cross-sectional study of the prevalence and correlates of genital warts among high-risk women in Mombasa, Kenya. Between 2001 and 2007, 1182 women were enrolled, of whom 613 (51.4%) were HIV-1 seropositive. Chi square tests and logistic regression were used to examine the associations between genital warts and potential correlates., Results: Genital warts were identified on clinical examination in 27 (2.3%) women. Women who were HIV-1 seropositive were nearly 8 times as likely to have genital warts compared with HIV-1-seronegative women (odds ratio, 7.69; 95% confidence interval, 2.30-25.6)., Conclusion: Understanding the prevalence and correlates of genital warts will help to determine whether coverage for the wart-inducing subtypes 6 and 11 in a human papillomavirus vaccine is an important consideration in resource-limited countries.