A Longitudinal Assessment of Cervical Inflammation and Immunity Associated with HIV-1 Infection, Hormonal Contraception, and Pregnancy.

Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t - 2, t - 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls. We measured 10 biomarkers of inflammation and immunity and used generalized linear models to estimate and compare biomarker levels across HIV status, contraceptive, and pregnancy groups. Biomarkers remained relatively stable across visits for controls, while in HIV-infected women cervical immunity started to change before seroconversion with RANTES and BD-2 increased and secretory leukocyte protease inhibitor (SLPI) decreased at t - 1 and continued to change at t0 with ICAM-1 up and IL-8 down and with more biomarkers after seroconversion (IL-1ß, IL-6, MIP-3α, VEGF, and IL-1RA down and IL-1RA:IL-1ß ratio up). In multivariable analyses, seroconverters had higher BD-2 at t - 1, higher RANTES and lower SLPI from t - 1 through t + 2, and lower IL-8 and IL-1RA at and/or after seroconversion compared to nonseroconverters. Compared to non-HC users, DMPA users had higher RANTES at all visits and lower BD-2 at t - 2 through t0, while COC users and pregnant women had higher IL-8 and SLPI at all visits; COC users also had lower BD-2 preseroconversion; pregnant women had lower RANTES at t0 - t + 2. Longitudinal patterns of cervical immunity differ between HIV seroconverters and HIV-negative women; seroconverters demonstrate increased RANTES and decreased SLPI starting before and continuing postseroconversion. Furthermore, these patterns are differentially regulated by DMPA, COC, and pregnancy.

Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

BACKGROUND: Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. METHODS AND FINDINGS: We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations. CONCLUSIONS: Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Assays for estimating HIV incidence: updated global market assessment and estimated economic value.

INTRODUCTION: Accurate incidence estimates are needed to characterize the HIV epidemic and guide prevention efforts. HIV Incidence assays are cost-effective laboratory assays that provide incidence estimates from cross-sectional surveys. We conducted a global market assessment of HIV incidence assays under three market scenarios and estimated the economic value of improved incidence assays. METHODS: We interviewed 27 stakeholders, and reviewed journal articles, working group proceedings, and manufacturers' sales figures. We determined HIV incidence assay use in 2014, and estimated use in 2015 to 2017 and in 5 to 10-years under three market scenarios, as well as the cost of conducting national and key population surveys using an HIV incidence assay with improved performance. RESULTS: Global 2014 HIV incidence assay use was 308,900 tests, highest in Asia and mostly for case- and population-based surveillance. Estimated 2015 to 2017 use was 94,475 annually, with declines due to China and the United States discontinuing incidence assay use for domestic surveillance. Annual projected 5 to 10 year use under scenario 1 - no change in technology - was 94,475. For scenario 2 - a moderately improved incidence assay - projected annual use was 286,031. Projected annual use for scenario 3 - game-changing technologies with an HIV incidence assay part of (a) standard confirmatory testing, and (b) standard rapid testing, were 500,000 and 180 million, respectively. As HIV incidence assay precision increases, decreased sample sizes required for incidence estimation resulted in $5 to 23 million annual reductions in survey costs and easily offset the approximately $3 million required to develop a new assay. CONCLUSIONS: Improved HIV incidence assays could substantially reduce HIV incidence estimation costs. Continued development of HIV incidence assays with improved performance is required to realize these cost benefits.

Hormonal contraception and area of cervical ectopy: a longitudinal assessment.

BACKGROUND: The effect of combined oral contraceptives (COCs) and depot-medroxyprogesterone acetate (DMPA) on the area of cervical ectopy is not well understood. STUDY DESIGN: From 1996 to 1999, we recruited women not using hormonal contraception from two family planning centers in Baltimore, MD. Upon study entry and 3, 6 and 12 months after the initial visit, participants were interviewed and received visual cervical examinations with photography. Ectopy was measured from digitized photographs and was analyzed both continuously and categorically (small [≤0.48 cm(2)] vs. large [>0.48 cm(2)]). RESULTS: Of 1003 enrolled women, 802 returned for at least one follow-up visit. At 12 months, the numbers of women using COCs, DMPA or no hormonal method at least 50% of the time since the prior visit were 230, 76 and 229, respectively. After multivariable adjustment, COC use (vs. no hormonal use) was associated with large area of ectopy (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.0-3.3). No significant relationship was observed between DMPA and large area of ectopy (OR: 0.5, 95% CI: 0.2-1.3). The incidence of large area of ectopy by contraceptive exposure (COC, DMPA or no hormonal method) was 17.4 (CI: 11.8-24.6), 10.9 (CI: 4.4-22.4) and 4.6 (CI: 2.2-8.4) per 100 woman-years, respectively. CONCLUSIONS: Use of COCs, but not DMPA, was associated with large area of cervical ectopy. Area of ectopy at baseline was the strongest predictor of area of ectopy at follow-up.

Assessment of the efficacy of the rectovaginal button fistula plug for the treatment of ileal pouch-vaginal and rectovaginal fistulas.

BACKGROUND: The treatment of rectovaginal and ileal pouch-vaginal fistulas remains a challenging problem for the colorectal surgeon. The aim of this study was to assess the short-term efficacy of the new Surgisis Biodesign rectovaginal button fistula plug in patients with such fistulas. METHODS: Between May 2008 and September 2008, patients with confirmed rectovaginal and ileal pouch-vaginal fistulas with backgrounds of inflammatory bowel disease were treated with the button fistula plug. The fistulas were assessed by magnetic resonance imaging and/or examination under anesthesia before the procedure. RESULTS: Twelve patients with a median age of 36 (range, 29-42) years underwent a total of 20 plug insertions. Five patients had confirmed rectovaginal fistulas and seven patients had ileal pouch-vaginal fistulas. At a median follow-up of 15 (interquartile range, 10-21) weeks, 7 of 12 patients (58%) had been treated successfully. Seven of the 20 plugs that were inserted (35%) were successful. This equates to the successful treatment of three of five (60%) of the rectovaginal fistulas, and four of seven (57%) of the ileal pouch-vaginal fistulas. Of the six patients who initially failed, a repeat procedure was performed of which one was successful. Two patients underwent a third repeat procedure, which was again unsuccessful in both cases. The success rate of these eight repeat plug insertions was therefore 12.5%. All plug failures were the result of dislodgement of the plug. There was no morbidity in our series. CONCLUSIONS: The new button fistula plug successfully treated 7 of 12 (58%) rectovaginal and ileal pouch-vaginal fistulas.

Audio computer-assisted self-interviewing in reproductive health research: reliability assessment among women in Harare, Zimbabwe.

PURPOSE: Research on the measurement of HIV risk demonstrates that interview mode can affect reporting; however, few studies have applied these findings to assessments of hormonal contraceptive use. This paper examines how audio computer-assisted self-interviewing (ACASI) influenced reports of hormonal contraceptive use and pregnancy among Zimbabwean women. METHODS: Using a prospective, randomized, cross-over design, we compared self-reports obtained with ACASI and face-to-face (FTF) interview among 655 women enrolled in a prospective study on hormonal contraceptive use and HIV acquisition. In addition, self-report data were compared to those collected during clinical exams. RESULTS: Compared to FTF interviews, reports of hormonal contraceptive use were lower in ACASI [odds ratio (OR)=0.6; 95% confidence interval (95% CI)=0.5-0.6], and reports of pregnancy were higher (OR=1.5; 95% CI=1.1-1.9). Both modes of self-report differed from records on contraceptive method disbursement. CONCLUSION: Although ACASI yielded higher reports of several reproductive health behaviors, discrepancies between self-reports and clinical data on method disbursement highlight persistent measurement challenges.