Letting HIV Transform Academia — Embracing Implementation Science

The human immunodeficiency virus (HIV) epidemic has had an extraordinary global impact. Even as it has devastated societies, it has also inspired community empowerment, motivated impressive scientific discoveries, and provoked an unprecedented mobilization of vast resources for a single health condition. Not yet fully realized, however, is the epidemic's potential for expanding the core mission of academic institutions to include the pursuit of a wider range of research

Incidence of sexually transmitted infections during pregnancy

Prevalence of sexually transmitted infections (STI) is high among pregnant women in certain settings. We estimated STI incidence and compared STI risk in pregnant and non-pregnant women. Data came from the Methods for Improving Reproductive Health in Africa (MIRA) study conducted in South Africa and Zimbabwe 2003–2006. Women aged 18–50 years with at least one follow-up visit within 6 months of enrollment were included. Follow-up visits included laboratory testing for pregnancy, chlamydia, gonorrhea, trichomoniasis, and HIV, as well as self-report of hormonal contraceptive (HC) use, sexual behaviors and intravaginal practices. All visits were classified according to pregnancy status. Incidence of each STI was calculated using follow-up time. Cox proportional hazards models were fitted using pregnancy as a time-varying exposure and sexual behaviors and intravaginal practices as time-varying covariates. Among 4,549 women, 766 (16.8%) had a positive pregnancy test. Median follow-up time was 18 months [IQR: 12–24]. The overall incidence rate of chlamydia was 6.7 per 100 person years (py) and 9.9/100py during pregnancy; gonorrhea incidence was 2.7/100py and 4.9/100py during pregnancy; trichomoniasis incidence was 7.1/100py overall and 9.2/100py during pregnancy. Overall HIV incidence was 3.9/100py and 3.8/100py during pregnancy. In crude models, pregnancy increased risk for chlamydia (hazard ratio (HR) 1.5, 95%CI: 1.1–1.2), however there was no increased risk of any measured STI in adjusted models. STI Incidence was high during pregnancy however pregnancy did not increase STI risk after adjustment for sexual behaviors. Greater efforts are needed to help pregnant women avoid STIs

Recent Patterns in Population-Based HIV Prevalence in Swaziland

Background: The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs. Methods: From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed. Results: HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use. Conclusions: While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland

Strategies for increasing impact, engagement, and accessibility in HIV prevention programs: suggestions from women in urban high HIV burden counties in the Eastern United States (HPTN 064)

Background Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US. Methods Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US. Results Thematic analyses revealed four themes describing women’s most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build “Market Demand”, and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources. Conclusions Findings may be useful for enhancing women’s engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors. Trial registration Clinicaltrials.gov: NCT00995176 , prospectively registered

Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064

Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009–2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1–4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Increased utilisation of PEPFAR-supported laboratory services by non-HIV patients in Tanzania

Background: It is unknown to what extent the non-HIV population utilises laboratories supported by the President’s Emergency Plan for AIDS Relief (PEPFAR). Objectives: We aimed to describe the number and proportion of laboratory tests performed in 2009 and 2011 for patients referred from HIV and non-HIV services (NHSs )in a convenience sample collected from 127 laboratories supported by PEPFAR in Tanzania. We then compared changes in the proportions of tests performed for patients referred from NHSs in 2009 vs 2011. Methods: Haematology, chemistry, tuberculosis and syphilis test data were collected from available laboratory registers. Referral sources, including HIV services, NHSs, or lack of a documented referral source, were recorded. A generalised linear mixed model reported the odds that a test was from a NHS. Results: A total of 94 132 tests from 94 laboratories in 2009 and 157 343 tests from 101 laboratories in 2011 were recorded. Half of all tests lacked a documented referral source. Tests from NHSs constituted 42% (66 084) of all tests in 2011, compared with 31% (29 181) in 2009. A test in 2011 was twice as likely to have been referred from a NHS as in 2009 (adjusted odds ratio: 2.0 [95% confidence interval: 2.0–2.1]). Conclusion: Between 2009 and 2011, the number and proportion of tests from NHSs increased across all types of test. This finding may reflect increased documentation of NHS referrals or that the laboratory scale-up originally intended to service the HIV-positive population in Tanzania may be associated with a ‘spillover effect’ amongst the general population

Retention Strategies and Factors Associated with Missed Visits Among Low Income Women at Increased Risk of HIV Acquisition in the US (HPTN 064)

Women at high-risk for HIV acquisition often face challenges that hinder their retention in HIV prevention trials. These same challenges may contribute to missed clinical care visits among HIV-infected women. This article, informed by the Gelberg-Andersen Behavioral Model for Vulnerable Populations, identifies factors associated with missed study visits and describes the multifaceted retention strategies used by study sites. HPTN 064 was a multisite, longitudinal HIV seroincidence study in 10 US communities. Eligible women were aged 18–44 years, resided in a census tract/zipcode with high poverty and HIV prevalence, and self-reported ≥1 personal or sex partner behavior related to HIV acquisition. Multivariate analyses of predisposing (e.g., substance use) and enabling (e.g., unmet health care needs) characteristics, and study attributes (i.e., recruitment venue, time of enrollment) identified factors associated with missed study visits. Retention strategies included: community engagement; interpersonal relationship building; reduction of external barriers; staff capacity building; and external tracing. Visit completion was 93% and 94% at 6 and 12 months. Unstable housing and later date of enrollment were associated with increased likelihood of missed study visits. Black race, recruitment from an outdoor venue, and financial responsibility for children were associated with greater likelihood of attendance. Multifaceted retention strategies may reduce missed study visits. Knowledge of factors associated with missed visits may help to focus efforts

Challenges of a Hidden Epidemic: HIV Prevention Among Women in the United States

HIV/AIDS trends in the United States depict a concentrated epidemic with hot spots that vary by location, poverty, race/ethnicity, and transmission mode. HIV/AIDS is a leading cause of death among US women of color; two thirds of new infections among women occur in black women, despite the fact that black women account for just 14% of the US female population. The gravity of the HIV epidemic among US women is often not appreciated by those at risk as well as by the broader scientific community. We summarize the current epidemiology of HIV/AIDS among US women and discuss clinical, research, and public health intervention components that must be brought together in a cohesive plan to reduce new HIV infections in US women. Only by accelerating research and programmatic efforts will the hidden epidemic of HIV among US women emerge into the light and come under control

Venue-Based Recruitment of Women at Elevated Risk for HIV: An HIV Prevention Trials Network Study

Background: The challenge of identifying and recruiting U.S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U.S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described. Methods: Eligible women were recruited from 10 U.S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18–44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual partner characteristic associated with HIV acquisition (e.g., incarceration history). Ethnography was conducted to finalize recruitment areas and venues. Results: Eight thousand twenty-nine women were screened and 2,099 women were enrolled (88% black, median age 29 years) over 14 months. The majority of participants were recruited from outdoor venues (58%), retail spaces (18%), and social service organizations (13%). The proportion of women recruited per venue category varied by site. Most participants (73%) had both individual and partner characteristics that qualified them for the study; 14% were eligible based on partner risk only. Conclusion: VBS is a feasible and effective approach to rapidly recruit a population of women at enhanced risk for HIV in the United States. Such a recruitment approach is needed in order to engage women most at risk and requires strong community engagement