OBJECTIVE To understand temporal trends in the contribution of different genital tract infections to HIV incidence over 20 years of follow-up in a cohort of high-risk women. DESIGN Prospective cohort study. METHODS We performed monthly evaluations for HIV, vaginal yeast, bacterial vaginosis (BV), Trichomonas vaginalis, Neisseria gonorrhoeae, non-specific cervicitis, herpes simplex virus type 2 (HSV-2), genital ulcer disease (GUD) and genital warts. We used Cox regression to evaluate the association between STIs and HIV acquisition over 4 time periods (1993–1997, 1998–2002, 2003–2007, 2008–2012). Models were adjusted for age, workplace, sexual risk behavior, hormonal contraceptive use, and other STIs. The resulting hazard ratios were used to calculate population attributable risk percent (PAR%). RESULTS Between 1993 and 2012, 1,964 women contributed 6,135 person-years of follow-up. The overall PAR% for each infection was: prevalent HSV-2 (48.3%), incident HSV-2 (4.5%), BV (15.1%), intermediate microbiota (7.5%), vaginal yeast (6.4%), T. vaginalis (1.1%), N. gonorrhoeae (0.9%), non-specific cervicitis (0.7%), GUD (0.8%), and genital warts (−0.2%). Across the four time periods, the PAR% for prevalent HSV-2 (40.4%, 61.8%, 58.4%, 48.3%) and BV (17.1%, 19.5%, 14.7%, 17.1%), remained relatively high and had no significant trend for change over time. The PAR% for trichomoniasis, gonorrhea, GUD and genital warts remained <3% across the four periods. CONCLUSIONS Bacterial vaginosis and HSV-2 have consistently been the largest contributors to HIV acquisition risk in the Mombasa Cohort over the past 20 years. Interventions that prevent these conditions would benefit women’s health, and could reduce their risk of becoming infected with HIV.

SUMMARYThree IgM monoclonal antibodies, M22G11P, M7B7 and M22B3G, which reacted with the surfaceof Schistosoma mansonischistosomula in an indirect fluorescent antibody assay, were found to recognize a polysaccharide-containing egg antigen previously designated K3. The monoclonal antibodies and a monospecific rabbit anti-K3serum also recognized a crossreacting antigen in a crude cercarial antigen preparation. In an eosinophil-mediated schistosomulum killing assay, all three monoclonal antibodies significantly inhibited the level of killing produced by human infection serum. An IgG3 monoclonal antibody, M22C1C, which also recognized the egg antigen K3, did not inhibit eosinophil-mediated killing. However, when lower concentrations of human serum were used in the assay, this monoclonal antibody significantly enhanced the level of killing, despite having no capacity to induce eosinophil-mediated damage in the absence of human infection serum. On the basis of these and other results we suggest the possibility that antibodies toS. mansoniegg antigens which cross-react with the surface of the early post-penetration schistosomulum may influence the effective expression of antibody-dependent, eosinophil-mediated effector mechanisms in human infections.

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IntroductionAdolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during risk periods is suboptimal. Judgemental interactions with healthcare workers (HCW) and inadequate counselling can be barriers to PrEP use among AGYW. Improving HCW competency and communication to support PrEP delivery to AGYW requires new strategies.Methods and analysisPrEP Implementation for Young Women and Adolescents Program-standardised patient (PrIYA-SP) is a cluster randomised trial of a standardised patient actor (SP) training intervention designed to improve HCW adherence to PrEP guidelines and communication skills. We purposively selected 24 clinics offering PrEP services under fully programmatic conditions in Kisumu County, Kenya. At baseline, unannounced SP ‘mystery shoppers’ present to clinics portraying AGYW in common PrEP scenarios for a cross-sectional assessment of PrEP delivery. Twelve facilities will be randomised to receive a 2-day training intervention, consisting of lectures, role-playing with SPs and group debriefing. Unannounced SPs will repeat the assessment in all 24 sites following the intervention. The primary outcome is quality of PrEP counselling, including adherence to national guidelines and communication skills, scored on a checklist by SPs blinded to intervention assignment. An intention-to-treat (ITT) analysis will evaluate whether the intervention resulted in higher scores within intervention compared with control facilities, adjusted for baseline SP scores and accounting for clustering by facility. We hypothesise that the intervention will improve quality of PrEP counselling compared with standard of care. Results from this study will inform guidelines for PrEP delivery to AGYW in low-resource settings and offer a potentially scalable strategy to improve service delivery for this high-risk group.Ethics and disseminationThe protocol was approved by institutional review boards at Kenyatta National Hospital and University of Washington. An external advisory committee monitors social harms. Results will be disseminated through peer-reviewed journals and presentations.Trial registration numberNCT03875950

fWe performed a case-control study of women at risk of HIV-1 superinfection to understand the relationship between immune activation and HIV-1 acquisition. An increase in the frequency of HIV-1 target cells, but not in other markers of T cell activation, was associated with a 1.7-fold increase in the odds of superinfection. This suggests that HIV-1 acquisition risk is influenced more by the frequency of target cells than by the generalized level of immune activation.