Applying the Functional Behavioral and Social Sciences Research (BSSR) Framework to HIV Cure Research

Introduction The search for an HIV cure involves important behavioural and social processes that complement the domains of biomedicine. However, the field has yet to tap into the full potential of behavioural and social sciences research (BSSR). In this article, we apply Gaist and Stirratt’s BSSR Functional Framework to the field of HIV cure research. Discussion The BSSR Functional Framework describes four key research domains: (1) basic BSSR (understanding basic behavioural and social factors), (2) elemental BSSR (advancing behavioural and social interventions), (3) supportive BSSR (strengthening biomedically focused clinical trials), and (4) integrative BSSR (building multi-disciplinary combination approaches for real-world implementation). In revisiting and applying the BSSR Functional Framework, we clarify the importance of BSSR in HIV cure research by drawing attention to such things as: how language and communication affect the meaning of “cure” to people living with HIV (PLHIV) and broader communities; how cure affects the identity and social position of PLHIV; counselling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision-making processes of potential study participants related to different cure strategies; HIV care providers’ perceptions and attitudes about their patients’ participation in cure research; potential social harms or adverse social events associated with cure research participation; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment. We also discuss the BSSR Functional Framework in the context of ATIs, which involve processes at the confluence of the BSSR domains. Conclusions To move HIV cure regimens through the translational research pathway, attention will need to be paid to both biomedical and socio-behavioural elements. BSSR can contribute an improved understanding of the human and social dimensions related to HIV cure research and the eventual application of HIV cure regimens. The BSSR Functional Framework provides a way to identify advances, gaps and opportunities to craft an integrated, multi-disciplinary approach at all stages of cure research to ensure the real-world applicability of any strategy that shows promise

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment

Program Spending to Increase Adherence: South African Cervical Cancer Screening

Background: Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa. Methodology/Principal Findings: We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence). Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14–R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12–R26). Conclusions/Significance: We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated

Improving Antiretroviral Therapy Adherence in Resource-Limited Settings at Scale: a Discussion of Interventions and Recommendations

INTRODUCTION: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. METHODS: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. RESULTS AND DISCUSSION: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. CONCLUSION: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS

Intravaginal and Menstrual Practices among Women Working in Food and Recreational Facilities in Mwanza, Tanzania: Implications for Microbicide Trials

Intravaginal and menstrual practices may potentially influence results of trials of microbicides for HIV prevention through effects on the vaginal environment and on adherence to microbicide and placebo products. As part of the feasibility study for the Microbicides Development Programme Phase 3 trial of a vaginal microbicide in Mwanza, a variety of quantitative and qualitative methods were used to describe these practices, associations with behaviour and underlying social norms among women working in food and recreational facilities. Intravaginal cleansing by inserting fingers and either water alone or soap and water was thought necessary to remove “uchafu” (dirt), referring to vaginal secretions, including menstrual blood and post-coital discharge. Vaginal cleansing was carried out within 2 hours after 45% of sex acts. Sexual enhancement practices were less common. Intravaginal and menstrual practices and associated behaviours and demographic factors should be measured and monitored throughout microbicide trials to enable analyses of their impacts on microbicide effectiveness

Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia

BACKGROUND: The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV) drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. METHODS: The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0) and third month (M3) follow up visits. RESULTS: A total of 400 and 383 patients at baseline (M0) and at follow up visit (M3) respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food) was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21). Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81). However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55) and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51) were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. CONCLUSION: The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot reliably be predicted by a few patient characteristics that are assumed to vary with time. Adherence is a process, not a single event, and adherence support should be integrated into regular clinical follow up

Impact of maternal ART on mother-to-child transmission (MTCT) of HIV at six weeks postpartum in Rwanda

BACKGROUND: In 2010, Rwanda adopted ART for prevention of mother to child transmission of HIV from pregnant women living with HIV during pregnancy and breasfeeding period. This study examines rates of mother-to-childtransmission of HIV at 6–10 weeks postpartum and risk factors for mother-to-child transmission of HIV (MTCT) among HIV infected women on ART during pregnancy and breastfeeding. METHODS: A cross-sectional survey study was conducted between July 2011–June 2012 among HIV-exposed infants aged 6–10 weeks and their mothers/caregivers. Stratified multi-stage, probability proportional to size and systematic sampling to select a national representative sample of clients. Consenting mothers/caregivers were interviewed on demographic and program interventions. Dry blood spots from HIV-exposed infants were collected for HIV testing using DNA PCR technique. Results are weighted for sample realization. Univariable analysis of socio-demographic and programmatic determinants of early mother-to-child transmission of HIV was conducted. Variables were retained for final multivariable models if they were either at least of marginal significance (p-value < 0.10) or played a confounding role (the variable had a noticeable impact > 10% change on the effect estimate). RESULTS: The study sample was 1639 infants with HIV test results. Twenty-six infants were diagnosed HIV-positive translating to a weighted MTCT estimate of 1.58% (95% CI 1.05–2.37%). Coverage of most elimination of MTCT (EMTCT) program interventions, was above 80, and 90.4% of mother-infant pairs received antiretroviral treatment or prophylaxis. Maternal ART and infant antiretroviral prophylaxis (OR 0.01; 95%CI 0.001–0.17) and maternal age older than 25 years were significantly protective (OR 0.33; 95%CI 0.14–0.78). No disclosure of HIV status, not testing for syphilis during pregnancy and preterm birth were significant risk factors for MTCT. Factors suggesting higher sociodemographic status (flush toilet, mother self-employed) were borderline risk factors for MTCT. CONCLUSION: ART for all women during pregnancy and breastfeeding was associated with the estimated low MTCT rate of 1.58%. Mothers who did not receive a full package of anti-retroviral therapy according to the Rwanda EMTCT protocol, and young and single mothers were at higher risk of MTCT and should be targeted for support in preventing HIV infection

A scoping review and thematic analysis of social and behavioural research among HIV-serodiscordant couples in high-income settings.

CAPRISA, 2015.Abstract available in pdf

Is forced migration a barrier to treatment success? Similar HIV treatment outcomes among refugees and a surrounding host community in Kuala Lumpur, Malaysia.

In response to an absence of studies among refugees and host communities accessing highly active antiretroviral therapy (HAART) in urban settings, our objective was to compare adherence and virological outcomes among clients attending a public clinic in Kuala Lumpur, Malaysia. A cross-sectional survey was conducted among adult clients (≥18 years). Data sources included a structured questionnaire that measured self-reported adherence, a pharmacy-based measure of HAART prescription refills over the previous 24 months, and HIV viral loads. The primary outcome was unsuppressed viral load (≥40 copies/mL). Among a sample of 153 refugees and 148 host community clients, refugees were younger (median age 35 [interquartile range, IQR 31, 39] vs 40 years [IQR 35, 48], p < 0.001), more likely to be female (36 vs 21 %, p = 0.004), and to have been on HAART for less time (61 [IQR 35, 108] vs 153 weeks [IQR 63, 298]; p < 0.001). Among all clients, similar proportions of refugee and host clients were <95 % adherent to pharmacy refills (26 vs 34 %, p = 0.15). When restricting to clients on treatment for ≥25 weeks, similar proportions from each group were not virologically suppressed (19 % of refugees vs 16 % of host clients, p = 0.54). Refugee status was not independently associated with the outcome (adjusted odds ratio, aOR = 1.28, 95 % CI 0.52, 3.14). Overall, the proportions of refugee and host community clients with unsuppressed viral loads and sub-optimal adherence were similar, supporting the idea that refugees in protracted asylum situations are able to sustain good treatment outcomes and should explicitly be included in the HIV strategic plans of host countries with a view to expanding access in accordance with national guidelines for HAART