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For women in the United States who remain sexually active beyond child-bearing years, susceptibility to HIV infection remains, yet condom use is low. We assessed acceptability of the dapivirine vaginal ring (ring) among 96 postmenopausal US women enrolled in a placebo-controlled multisite phase II trial of the ring, using questionnaires and in-depth interviews. Three quarters of women reported "perfect" adherence (ring never out) over the 3-month trial period. At study exit, the ring was found to be very easy to use by 72%, very comfortable to wear by 65%, and 4% reported it ever interfered with their daily activities. The most common worries among participants at preinitiation had decreased significantly at study exit (e.g., worries about inserting the ring declined from 46% to 6%, discomfort during daily activities from 53% to 3%, ring not staying in place from 48% to 14%, all p < 0.0001). Despite some couples feeling the ring during sex, the ring was perceived as more suitable than condoms for prevention because it was not burdensome to use, did not interfere with erection, and provided (for some) additional vaginal lubrication. The ring is a promising, highly acceptable HIV prevention method that is suitable to the lives of postmenopausal women and their male partners and can provide them with an additional prevention choice. Clinical Trials Registration: NCT02010593. [ABSTRACT FROM AUTHOR]

Background Postmenopausal women have unique sociobiological human immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics, and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus placebo in postmenopausal women. Methods We enrolled 96 HIV-negative postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We assessed safety by adverse events (AEs). DPV concentrations were quantified in plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and 12 weeks using repeated measures ANOVA. We assessed acceptability by self-report. Results We found no differences in the proportion of women with related grade 2 or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P =.68) or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P =.57). In the DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high; 84/93 (90%) "very much liked or liked" the VR. Conclusions DPV VRs were safe, well tolerated, and acceptable in postmenopausal women. Plasma concentrations were comparable to published data on DPV use in reproductive-age women (median plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic data, the DPV VR is promising for preexposure prophylaxis in postmenopausal women. Clinical Trials Registration NCT02010593. [ABSTRACT FROM AUTHOR]

We evaluated the adherence and acceptability of a vaginal ring containing dapivirine, maraviroc, or both drugs for 28 days during a Phase I placebo-controlled trial in 48 HIV-negative sexually abstinent U.S. women aged 18-40. Adherence was assessed weekly by clinical interview and computer-assisted self-interviewing; acceptability assessment occurred at the last product-use visit. Study retention was 98 % (47/48); 94 % (45/48) reported being fully adherent with ring use during the 28-day period. Two participants experienced the ring partially coming out. Analysis was blinded and behavioral data were combined across study groups. Most women reported being very comfortable having the ring in their vagina; 44 % preferred continuous use, whereas 51 % had no preference compared to episodic use. Although a range of minor ring concerns were expressed, few were actually experienced. High adherence to and acceptability of this vaginal ring in this Phase I trial contributes to its promise as a sustained mechanism for multidrug vaginal microbicide delivery. [ABSTRACT FROM AUTHOR]

Background: We sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the US. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework.Methods: We gathered qualitative data (120 interviews and 31 focus groups) from a subset of women ages 18-44 years (N = 2,099) enrolled in the HPTN 064 HIV seroincidence estimation study across 10 US communities. We analyzed data from 4 diverse locations: Atlanta, New York City (the Bronx), Raleigh, and Washington, DC. Data were thematically coded using grounded theory methodology. Intercoder reliability was assessed to evaluate consistency of team-based coding practices.Results: The following themes were identified at 4 levels including 1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; 2) mesosystem (network): organizational social support and sexual concurrency; 3) microsystem (dyadic): sex exchange, interpersonal social support, intimate partner violence; and 4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risk-taking behavioral pathways.Conclusions: Multilevel syndemic factors contribute to women's vulnerability to HIV in the US. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk.Trial Registration: Clinicaltrials.gov, NCT00995176. [ABSTRACT FROM AUTHOR]

Knowledge of sexual partners' HIV infection can reduce risky sexual behaviors. Yet, there are no published studies to-date examining prevalence and characteristics associated with knowledge among African-American women living in high poverty communities disproportionately affected by HIV. Using the HIV Prevention Trial Network's (HPTN) 064 Study data, multivariable logistic regression was used to examine individual, partner, and partnership-level determinants of women's knowledge (n = 1,768 women). Results showed that women's demographic characteristics alone did not account for the variation in serostatus awareness. Rather, lower knowledge of partner serostatus was associated with having two or more sex partners (OR = 0.49, 95 % CI 0.37-0.65), food insecurity (OR = 0.68, 95 % CI 0.49-0.94), partner age >35 years (OR = 0.68, 95 % CI 0.49-0.94), and partner concurrency (OR = 0.63, 95 % CI 0.49-0.83). Access to financial support (OR = 1.42, 95 % CI 1.05-1.92) and coresidence (OR = 1.43, 95 % CI 1.05-1.95) were associated with higher knowledge of partner serostatus. HIV prevention efforts addressing African-American women's vulnerabilities should employ integrated behavioral, economic, and empowerment approaches. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We compared adherence to and acceptability of daily topical and oral formulations of tenofovir (TFV) used as pre-exposure prophylaxis (PrEP) for HIV prevention among women in South Africa, Uganda and the United States. 144 sexually active, HIV-uninfected women participated in a cross-over study of three regimens: oral tablet, vaginal gel, or both. We tested for differences in adherence and evaluated product acceptability. Self-reported adherence for all regimens was high (94 %), but serum TFV concentrations indicated only 64 % of participants used tablets consistently. Most women in the U.S. (72 %) favored tablets over gel; while preferences varied at the African sites (42 % preferred gel and 40 % tablets). Findings indicate a role for oral and vaginal PrEP formulations and highlight the importance of integrating pharmacokinetics-based adherence assessment in future trials. Biomedical HIV prevention interventions should consider geographic and cultural experience with product formulations, partner involvement, and sexual health benefits that ultimately influence use. [ABSTRACT FROM AUTHOR]

Background: Women account for 23% of newly diagnosed HIV infections in the United States, but there are few recent, well-characterized cohorts of U.S. women in whom behavior character-istics and HIV acquisition have been well-described. Objective: To evaluate HIV incidence and describe behaviors among U.S. women residing in areas of high HIV prevalence. Design: Multisite, longitudinal cohort of women who had HIV rapid testing and audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months. (ClinicalTrials.gov: NCT00995176) Setting: 10 urban and periurban communities with high HIV prev-alence and poverty rates, located in the northeastern and south-eastern United States. Patients: Venue-based sampling was used to recruit women aged 18 to 44 years who recently had unprotected sex and had 1 or more additional personal or partner risk factors and no self-reported previous HIV diagnosis Measurements: HIV prevalence and incidence, frequency of HIV risk behaviors, and health status perceptions. Results: Among 2099 high-risk women (85.9% black and 11.7% of Hispanic ethnicity), 32 (1.5%) were diagnosed with HIV infec-tion at enrollment. Annual HIV incidence was 0.32% (95% CI, 0.14% to 0.74%). Older age, substance use, and knowing a part-ner had HIV were associated with HIV prevalence. Ten women died during the study (0.61 % per year). Limitations: Longitudinal assessment of risk behaviors was limited to a maximum of 12 months. There were few incident HIV infec-tions, precluding identification of characteristics predictive of HIV acquisition. Conclusion: This study enrolled a cohort of women with HIV incidence substantially higher than the Centers for Disease Control and Prevention national estimate in the general population of U.S. black women. Concerted efforts to improve preventive health care strategies for HIV and overall health status are needed for similar populations. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on some of the health care concerns of Hispanics and Latinos and the creation of the Surgeon General's National Hispanic-Latino Health Initiative. The initiative's threefold purpose; Strategies to foster health promotion and disease prevention; More.

Abstract: Background: Substance use is associated with HIV sexual risk behaviors, yet few studies have examined substance use patterns longitudinally. We evaluated the types and frequency of substances used over a six-month period among U.S. women at risk for HIV acquisition. Methods: Women reporting unprotected sex with a man in the previous six months and at least one other personal or partner HIV risk characteristic enrolled in a multisite cohort study and completed interviews about substance use at study visits. Prevalence and frequency of substance use at the baseline and six-month visits were compared and correlates of decreased substance use at the six-month visit were assessed. Results: Of 2099 women enrolled, 1882 had substance use data at baseline and six-months. Of these, 76.1% reported using at least one drug or binge drinking in the previous six months; 37.5% were frequent and 38.6% non-frequent substance users. Binge drinking was most frequently reported (63.3%), followed by cocaine (25.0%) and opioids (16.5%). Fifty-five percent of opiate users and 30% of cocaine users reported daily/almost daily use. At the six-month visit, 40.5% reported a decrease in frequency of use. Adjusting for income and type of drug used, poly-substance users were less likely to decrease frequency of use compared to those who only used one substance. Conclusion: A substantial decrease in frequency of substance use over time was observed in this cohort. Poly-substance users were less likely to reduce frequency of use over time, suggesting that specific substance use interventions targeting these users are warranted. [Copyright &y& Elsevier]

The article presents a study of the human immunodeficiency virus (HIV) prevention among women in the U.S. The study summarizes the epidemiology of HIV and acquired immune deficiency syndrome (AIDS) among women in the country. It also discusses the public health intervention components needed in the reduction of new HIV infections.

Background: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence., Methods: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews., Results: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits., Conclusion: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.

Objectives: We determined the prevalence of recent emotional, physical, and sexual violence against women and their associations with HIV-related risk factors in women living in the United States., Methods: We performed an assessment of women ages 18 to 44 years with a history of unprotected sex and 1 or more personal or partner HIV risk factors in the past 6 months from 2009 to 2010. We used multivariable logistic regression to examine the association of experiencing violence., Results: Among 2099 women, the prevalence of emotional abuse, physical violence, and sexual violence in the previous 6 months was 31%, 19%, and 7%, respectively. Nonmarried status, food insecurity, childhood abuse, depression symptomology, and posttraumatic stress disorder were significantly associated with multiple types of violence. All types of violence were associated with at least 3 different partner or personal HIV risk behaviors, including unprotected anal sex, previous sexually transmitted infection diagnosis, sex work, or partner substance abuse., Conclusions: Our data suggested that personal and partner HIV risk behaviors, mental illness, and specific forms of violence frequently co-occurred in the lives of impoverished women. We shed light on factors purported to contribute to a syndemic in this population. HIV prevention programs in similar populations should address these co-occurring issues in a comprehensive manner.

Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community's HIV/STI risk. We explored perceptions of community HIV/STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women's HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/STI risk driven by structural factors.

Purpose: Reductions in risk behaviors are common following enrollment in human immunodeficiency virus (HIV) prevention studies. We develop methods to quantify the proportion of change in risk behaviors that can be attributed to regression to the mean versus study participation and other factors., Methods: A novel model that incorporates both regression to the mean and study participation effects is developed for binary measures. The model is used to estimate the proportion of change in the prevalence of "unprotected sex in the past 6 months" that can be attributed to study participation versus regression to the mean in a longitudinal cohort of women at risk for HIV infection who were recruited from ten U.S. communities with high rates of HIV and poverty. HIV risk behaviors were evaluated using audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months., Results: The prevalence of "unprotected sex in the past 6 months" declined from 96% at baseline to 77% at 12 months. However, this change could be almost completely explained by regression to the mean., Conclusions: Analyses that examine changes over time in cohorts selected for high- or low- risk behaviors should account for regression to the mean effects., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Objectives: We examined parameters of sexual partnerships, including respondents' participation in concurrency, belief that their partner had concurrent partnerships (partners' concurrency), and partnership intervals, among the 2099 women in HIV Prevention Trials Network 064, a study of women at high risk for HIV infection, in 10 U.S. communities., Methods: We analyzed baseline survey responses about partnership dates to determine prevalence of participants' and partners' concurrency, intervals between partnerships, knowledge of whether recent partners had undergone HIV testing, and intercourse frequency during the preceding 6 months., Results: Prevalence of participants' and partners' concurrency was 40% and 36%, respectively; 24% respondents had both concurrent partnerships and nonmonogamous partners. Among women with >1 partner and no concurrent partnerships themselves, the median gap between partners was 1 month. Multiple episodes of unprotected vaginal intercourse with ≥2 of their most recent partners was reported by 60% of women who had both concurrent partnerships and nonmonogamous partners, 50% with only concurrent partners and no partners' concurrency, and 33% with only partners' concurrency versus 14% of women with neither type of concurrency (P < 0.0001). Women who had any involvement with concurrency were also more likely than women with no concurrency involvement to report lack of awareness of whether recent partners had undergone HIV testing (participants' concurrency 41%, partners' concurrency 40%, both participants' and partners' concurrency 48%, neither 17%; P < 0.0001)., Conclusions: These network patterns and short gaps between partnerships may create substantial opportunities for HIV transmission in this sample of women at high risk for HIV infection.

Background: Historically, four divisions of the National Institute of Allergy and Infectious Diseases (NIAID) that manage clinical trials and oversee data and safety monitoring have operated fairly autonomously with respect to their approaches to Data and Safety Monitoring Board (DSMB) operations. We recognized the need for a revised policy on DSMB operations in an effort to encourage greater harmonization of procedures across the four divisions., Purpose: The purpose of this article is to describe the considerations that motivated the development of the new policy, summarize current DSMB policies and ongoing harmonization efforts across the four divisions, and offer some recommendations for DSMB operations in the hope that other organizations may benefit from our experience., Methods: From 2005 to 2009, a working group undertook a review of DSMB responsibilities, policies, and operations. We analyzed and summarized the final policy document that the working group produced, gathered data describing current DSMB activities, and developed a tabular, cross-sectional overview highlighting how divisions are harmonizing their DSMB operations., Results: In 2010, there were 44 DSMBs in NIAID monitoring 169 protocols, and those DSMBs conducted 209 reviews of the protocols. Review and analysis of DSMB practices across the four divisions have led to recommendations for efficient and successful DSMB operations: adopt an inclusive approach, whereby the trial investigators assist in the process of forming and utilizing DSMBs; structures other than DSMBs can often provide many of the features of DSMBs but with greater flexibility in membership, access to interim data, and scheduling; the trial protocol should specify what safety and other concerns should trigger a DSMB review and what data should be included in prespecified reviews; present data in thoughtful and user-friendly ways that answer specific questions; allow sufficient time to plan for working with the DSMB., Limitations: We recognize that NIAID's specific circumstances and DSMB policy may not apply to the operation of DSMBs in every organization. Nevertheless, we believe that useful lessons can be learned from our experiences and efforts toward harmonization., Conclusions: Homogeneity in DSMB operations and management has appeal as a matter of organizational policy and efficiency. Some limited flexibility, as long as it honors fundamental principles of independence, confidentiality of interim trial results, and clear lines of reporting and approval, may be appropriate on occasion. NIAID's 2009 institute-level policy established a collective understanding of the important contribution that DSMBs make to the responsible conduct of clinical trials. Thinking will continue to evolve, leading to further policy refinements and the continued assurance of patient safety in our clinical trials.

Objective: To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission., Design: Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm., Methods: Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up., Results: The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89)., Conclusion: The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.