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We are grateful to Sharon Achilles for her thoughtful input related to describing potential biological mechanisms, and to all study investigators who provided additional information about their analyses. WHO provided support for the writing of this systmatic review and for the writing group to attend a working meeting in Geneva, Switzerland in October 2015. D.J.W. was partially funded by NIH DP2-HD-08-4070. The review was conducted independently of the WHO guidance development process; and conclusions represent the independent opinions of the authors. The findings and conclusions in this article do not necessarily reflect the positions and policies of the donor. Role of authors: The World Health Organization (J.N.K. and P.S.S.) initiated the idea to conduct this systematic review update. C.B.P. led the conduct of the systematic review, including conducting the systematic literature search and drafting the manuscript. C.B.P., K.M.C., and P.C.H. screened titles, abstracts, and full-text manuscripts to determine study inclusion. S.J.P. conducted the statistical meta-analysis. All coauthors (C.B.P., K.M.C., P.C.H., S.J.P., T.C., J.N.K., D.J.W., and P.S.S.) participated in framing the study question, developing the quality criteria, abstracting study information and assessing study quality, interpreting the data, and contributing to the writing and editing of the manuscript. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Guttmacher Institute, the Centers for Disease Control and Prevention, the World Health Organization, the National Institutes of Health, or other institutions with which the authors are affiliated.

OBJECTIVE: The objective of this study was 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: A prospective cohort study. METHODS: We performed monthly evaluations for HIV vaginal yeast bacterial vaginosis Trichomonas vaginalis Neisseria gonorrhoeae nonspecific cervicitis herpes simplex virus type two (HSV-2) genital ulcer disease (GUD) and genital warts. We used Cox regression to evaluate the association between sexually transmitted infections (STIs) and HIV acquisition over four time periods (1993-1997 1998-2002 2003-2007 2008-2012). Models were adjusted for age workplace sexual risk behaviour hormonal contraceptive use and other STIs. The resulting hazard ratios were used to calculate population attributable risk percentage (PAR%). RESULTS: Between 1993 and 2012 1964 women contributed 6135 person-years of follow-up. The overall PAR% for each infection was prevalent HSV-2 (48.3%) incident HSV-2 (4.5%) bacterial vaginosis (15.1%) intermediate microbiota (7.5%) vaginal yeast (6.4%) T. vaginalis (1.1%) N. gonorrhoeae (0.9%) nonspecific 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 bacterial vaginosis (17.1% 19.5% 14.7% 17.1%) remained relatively high and had no significant trend for change over time. The PAR% for trichomoniasis gonorrhoea GUD and genital warts remained less than 3% across the four periods. CONCLUSION: 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 womens health and could reduce their risk of becoming infected with HIV.

Objective To evaluate preexposure prophylaxis (PrEP) efficacy for HIV-1 prevention among women using depot medroxyprogesterone acetate (DMPA) for contraception and men whose HIV-1-infected partners use DMPA. Design Secondary analysis of data from a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among heterosexual Kenyan and Ugandan HIV-1 serodiscordant couples. Methods PrEP efficacy for HIV-1 prevention was compared among HIV-1-uninfected women using DMPA versus no hormonal contraception and among HIV-1 uninfected men whose HIV-1-infected female partners used DMPA versus no hormonal contraception. Results Of 4747 HIV-1 serodiscordant couples, 901 HIV-1-uninfected women used DMPA at some point during follow-up, 1422 HIV-1-uninfected women used no hormonal contraception, 1568 HIV-1-uninfected men had female partners who used DMPA, and 2626 men had female partners who used no hormonal contraception. PrEP efficacy estimates for HIV-1 prevention, compared with placebo, were similar among women using DMPA and those using no hormonal contraception (64.7 and 75.5%, adjusted interaction P = 0.65). Similarly, for men whose female partners used DMPA, PrEP efficacy did not differ from men whose partners used no hormonal contraception (90.0 versus 81.7%, adjusted interaction P = 0.52). Conclusion PrEP is efficacious for HIV-1 prevention among women using DMPA and men whose partners use DMPA, suggesting PrEP could mitigate the potential increased HIV-1 acquisition and transmission risks that have been associated with DMPA use. Women at risk for HIV-1 choosing DMPA could maintain this contraceptive method and add PrEP to achieve prevention of unintended pregnancy and HIV-1.

Background: HIV testing male partners of pregnant women may decrease HIV transmission to women and promote uptake of prevention of mother-to-child HIVtransmission (PMTCT) interventions. However it has been difficult to access male partners in antenatal care (ANC) clinics. We hypothesized that home visits to offer HIV testing to partners of women attending ANC would increase partner HIV testing. Methods: Women attending their first ANC were enrolled interviewed using smartphone audio-computer-assisted self-interviews and randomized to home visits or written invitations for male partners to come to clinic if they were married or cohabiting unaccompanied by partners and had no prior couple HIVcounselling and testing (CHCT). Enrolled men were offered CHCT (HIV testing and mutual disclosure). Prevalence of CHCT male HIV seropositivity couple serodiscordance and intimate partner violence reported as physical threat from partner were compared at 6 weeks. Results: Among 495 women screened 312 were eligible and 300 randomized to clinic-based or home-based CHCT. Median age was 22 years (interquartile range 20-26 years) and 87% were monogamous. CHCT was significantly higher in home-visit than in clinic-invitation arm (n=128 85% vs. n=54 36%; P

BACKGROUND: Intimate partner violence (IPV) is common worldwide and is an important consideration in couples HIV voluntary counseling and testing (CVCT) especially for HIV-serodiscordant couples (i.e. in which only one member is HIV-infected). DESIGN: Prospective study of 3408 HIV-serodiscordant couples (2299 in which the HIV-infected partner was female) from seven countries from East and Southern Africa. METHODS: At quarterly visits during up to 2 years of follow-up participants were asked separately about IPV perpetrated against them by their partner during the prior 3 months. Correlates of IPV were determined by generalized estimating equations. RESULTS: The majority of couples were married and living together with an average duration of partnership of approximately 5 years. More than 39000 quarterly visits were recorded. IPV was reported in 2.7% of visits by HIV-infected women 2.2% by HIV-uninfected women 0.9% by HIV-infected men and 0.7% by HIV-uninfected men. The majority of IPV reports were verbal or a combination of verbal and physical violence. Those who were HIV-infected were more likely to report IPV [for women adjusted odds ratio (AOR) 1.33 P = 0.043; for men AOR 2.20 P = 0.001] but IPV was not significantly associated with risk of HIV seroconversion in HIV-uninfected participants. IPV incidence decreased during follow-up (P < 0.001). CONCLUSION: During up to 2 years of prospective follow-up most persons in stable HIV-serodiscordant partnerships who had undergone CVCT did not report IPV. A modest increased risk of IPV was seen for HIV-infected partners both female and male.

BACKGROUND The effects of short-course antiretrovirals given to reduce mother-to-child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and DNA in breast milk are not well defined. METHODS Women in Kenya received short-course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or short-course highly active antiretroviral therapy (HAART). Breast milk samples were collected two to three times weekly for 4-6 weeks. HIV-1 DNA was quantified by real-time PCR. Cell-free and cell-associated RNA levels were quantified by the Gen-Probe HIV-1 viral load assay. RESULTS Cell-free HIV-1 RNA levels in breast milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared with ZDV between day 3 and week 4 postpartum (P < or = 0.03). Breast milk HIV-1 DNA levels (infected cell levels) were not significantly different between treatment arms at any timepoint during the 4-6-week follow-up. At 3 weeks postpartum, when the difference in cell-free RNA levels was the greatest comparing HAART directly with ZDV (P = 0.0001), median log10 HIV-1 DNA copies per 1 x 10 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and HAART arms, respectively (P = 0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P = 0.04), as well as over time according to a linear mixed-effects model. CONCLUSION Cell-free and, to a lesser extent, cell-associated HIV-1 RNA levels in breast milk were suppressed by antiretroviral regimens used to prevent MTCT. However, even with HAART, there was no significant reduction in the reservoir of infected cells, which could contribute to breast milk HIV-1 transmission.