James Kiarie

Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting.

Background Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis. Methods and Findings WHO’s 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15–49 years, the estimated global prevalence of chlamydia was 4.2% (95% uncertainty interval (UI): 3.7–4.7%), gonorrhoea 0.8% (0.6–1.0%), trichomoniasis 5.0% (4.0–6.4%), and syphilis 0.5% (0.4–0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0–3.6%), gonorrhoea 0.6% (0.4–0.9%), trichomoniasis 0.6% (0.4–0.8%), and syphilis 0.48% (0.3–0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100–166 million), 78 million of gonorrhoea (53–110 million), 143 million of trichomoniasis (98–202 million), and 6 million of syphilis (4–8 million). Prevalence and incidence estimates varied by region and sex. Conclusions Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

Objective and design:Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase womens HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data. Methods:We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception. Results:We identified 10 new reports of which five were considered ‘unlikely to inform the primary question’. We focus on the other five reports, along with nine from the previous review, which were considered ‘informative but with important limitations’. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4. Conclusion:Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.

The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps

In 2014, the World Health Organization, the US National Institutes of Health, and global technical partners published a comprehensive roadmap for development of new vaccines against sexually transmitted infections (STIs). Since its publication, progress has been made in several roadmap activities: obtaining better epidemiologic data to establish the public health rationale for STI vaccines, modeling the theoretical impact of future vaccines, advancing basic science research, defining preferred product characteristics for first-generation vaccines, and encouraging investment in STI vaccine development. This article reviews these overarching roadmap activities, provides updates on research and development of individual vaccines against herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and discusses important next steps to advance the global roadmap for STI vaccine development.

Unreported antiretroviral use by HIV-1-infected participants enrolling in a prospective research study

The concentration of viral RNA in plasma is the primary risk factor for sexual transmission of HIV-1 [1–3], and reductions in plasma HIV-1 RNA levels due to antiretroviral therapy (ART) result in marked decreases in HIV-1 transmission risk [4,5]. Results from studies of HIV-1 transmission and disease progression may be more difficult to interpret if a substantial proportion of HIV-1 infected partners have low or undetectable viral loads on ART, and thus, ART use at study enrollment is often an exclusion factor.

Daily Acyclovir to Decrease Herpes Simplex Virus Type 2 (HSV-2) Transmission from HSV-2/HIV-1 Coinfected Persons: A Randomized Controlled Trial

BACKGROUND Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown. METHODS Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1-infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1-susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission. RESULTS We randomly assigned 911 HSV-2/HIV-1-serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval, .83-2.20]; P = .22). Among HSV-2-susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2-susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016). CONCLUSIONS Treatment of African HSV-2/HIV-1-infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1-infected persons are needed.

HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy

Objective:Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression. Design:Prospective cohort study. Methods:Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and generalized estimating equations logistic regression. Results:The cumulative probabilities of achieving blood viral suppression (<80 copies per milliliter) 3, 6, and 9 months after ART initiation were 65.3%, 84.8%, and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6 months of ART. Pregnancy incidence was 8.8 per 100 person-years during the first 6 months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0–6 months after ART initiation (3 infections; 168 person-years), and 0.00 with >6 months of ART (0 infections; 167 person-years). Conclusions:Residual HIV transmission risk persists during the first 6 months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved.

Reversibility of Glomerular Renal Function Decline in HIV-Uninfected Men and Women Discontinuing Emtricitabine-Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis.

Background:Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the reversibility of eGFR decline among HIV-uninfected adults discontinuing PrEP. Methods:Data were from the Partners PrEP Study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women with baseline creatinine clearance ≥60 mL/min. Serum creatinine was measured quarterly while on-study medication and at month 1 and 2 after discontinuation. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation. Results:A total of 3924 individuals had a poststudy drug serum creatinine measurement after the scheduled drug discontinuation (1271 for TDF, 1308 for FTC-TDF, and 1345 for placebo); 65% were men, median age was 35 (range 18–64) years. Median time on study drug was 33 (interquartile range 25–36) months overall, and 36 months (interquartile range 30–36) for TDF and FTC-TDF. Mean eGFR at the last on-treatment visit was 129 mL·min−1·1.73 m−2 for TDF and 128 mL·min−1·1.73 m−2 for FTC-TDF versus 131 mL·min−1·1.73 m−2 for placebo (2–3 mL·min−1·1.73 m−2 mean decline for PrEP versus placebo, P ⩽ 0.01), and this difference reversed by 4 weeks after drug discontinuation (mean eGFR at the first postdrug visit: 130 mL·min−1 1.73 m−2 in all groups). More than 96% of participants had a confirmed >75% eGFR rebound to baseline level by 8 weeks after drug discontinuation, with similar proportions across treatment groups. Conclusions:In this large, placebo-controlled study of TDF-based PrEP, the small reduction in mean eGFR associated with PrEP reversed within weeks after discontinuation.

Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012.

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.

Preexposure prophylaxis is efficacious for HIV-1 prevention among women using depot medroxyprogesterone acetate for contraception.

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.

Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples

BACKGROUND A heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons. METHODS Using prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1-susceptible and HIV-1-infected partners. Plasma was collected before seroconversion for cases. RESULTS For both HIV-1-infected and HIV-1-susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T(2) test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1-susceptible and HIV-1-infected case partners, compared with HIV-1-susceptible and HIV-1-infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1-susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1-infected partners (P = .02). CONCLUSIONS Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.