Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men.

Measurement of adherence to oral pre-exposure prophylaxis (PrEP) in real-time has been challenging. We developed DOT Diary, a smartphone application that combines automated directly observed therapy with a PrEP adherence visualization toolkit, and tested its ability to measure PrEP adherence and to increase adherence among a diverse cohort of young men who have sex with men (MSM). We enrolled 100 MSM in San Francisco and Atlanta and randomly assigned them 2:1 to DOT Diary versus standard of care. Concordance between DOT Diary measurement and drug levels in dried blood spots was substantial, with 91.0% and 85.3% concordance between DOT Diary and emtricitabine-triphosphate and tenofovir-diphosphate, respectively. There was no significant difference in the proportion of participants with detectable PrEP drug levels at 24 weeks between study arms. These results suggest DOT Diary is substantially better than self-reported measures of adherence, but additional interventions are needed to improve PrEP adherence over time.

RESUMEN: La medición de la adherencia a la profilaxis oral previa a la exposición (PrEP) en tiempo real ha constituido un desafío. Hemos desarrollado DOT Diary, una aplicación para teléfonos inteligentes que combina la terapia automatizada observada de forma directa con un kit de herramientas para visualizar la adherencia a la PrEP, y testeamos su capacidad para medir la adherencia a la PrEP, así como para aumentar la adherencia entre una cohorte variada de hombres jóvenes que tienen sexo con hombres (HSH). Reclutamos a 100 HSH en San Francisco y Atlanta y los asignamos aleatoriamente 2:1 a DOT Diary con respecto a la asistencia estándar. La concordancia entre la medición del DOT Diary y los niveles de fármacos en gotas de sangre seca fue sustancial, con un 91,0% y un 85,3% de concordancia entre el uso del DOT Diary y el de emtricitabina-trifosfato y tenofovir-difosfato, respectivamente. No hubo diferencias significativas en la proporción de participantes con niveles detectables del fármaco de la PrEP a las 24 semanas entre los brazos del estudio. Estos resultados sugieren que DOT Diary es sustancialmente superior a las medidas de adherencia que se notifican de forma personal, aunque hacen falta intervenciones adicionales para mejorar la adherencia a la PrEP a largo plazo.

DOT Diary: Developing a Novel Mobile App Using Artificial Intelligence and an Electronic Sexual Diary to Measure and Support PrEP Adherence Among Young Men Who Have Sex with Men.

Young men who have sex with men (YMSM) are highly vulnerable to HIV. While pre-exposure prophylaxis (PrEP) has demonstrated effectiveness, adherence has been low among YMSM and difficult to measure accurately. In collaboration with a healthcare company, we configured an automated directly-observed therapy (aDOT) platform for monitoring and supporting PrEP use. Based on interest expressed in focus groups among 54 YMSM, we combined aDOT with an electronic sexual diary to provide feedback on level of protection during sex and to motivate app use. In an 8-week optimization pilot with 20 YMSM in San Francisco and Atlanta, the app was found to be highly acceptable, with median System Usability Scale scores in the "excellent" range (80/100). App use was high, with median PrEP adherence of 91% based on aDOT-confirmed dosing. Most (84%) participants reported the app helped with taking PrEP. These promising findings support further evaluation of DOT Diary in future effectiveness studies.

Understanding PrEP Persistence: Provider and Patient Perspectives.

PrEP persistence, or PrEP use over time, has been shown to be short, with most PrEP users stopping within 6-12 months. Furthermore, those most vulnerable to HIV often use PrEP for shorter periods. This qualitative study explores patient, provider, and contextual factors that influence PrEP persistence. In interviews with 25 PrEP users and 18 PrEP providers in San Francisco's safety net clinics, we analyze the perceived benefits and difficulties of taking PrEP, including structural barriers. We identify different steps in receipt of PrEP care (clinic visits and lab tests, pharmacy interactions, and medication adherence), and describe barriers and facilitators for providers and patients at each step. Our findings suggest that drop-in visits, streamlined testing, standing orders for labs, and 90-day PrEP prescriptions are highly desirable for many PrEP users. Also important are the proactive provision of adherence support and counseling, and referrals for housing, substance use, and mental health services.

Transition to a 1-year deferral for male blood donors who report sexual contact with men: staff perspectives at one blood collection organization.

BACKGROUND: Front-line staff at blood collection organizations (BCOs) play important roles in keeping the blood supply safe, yet research on their professional practice and perspectives on training needs is sparse. This qualitative study explored these topics with regard to the then-impending change in donor eligibility for men reporting sex with another man (MSM). STUDY DESIGN AND METHODS: Semistructured, individual interviews with BCO staff (n = 13) in Northern California covered experiences of and opinions on indefinite deferral, the revised 1-year deferral, and anticipated potential challenges arising from the new policy. Transcripts were thematically coded, using deductive and inductive approaches. Analysis identified recurrent and divergent themes. RESULTS: Interviewees reported strong values of professionalism and respect for donors and supported the change to a 1-year deferral for MSM donors. Nonetheless, nearly all voiced the need for more in-depth training to maximize the likelihood of successful implementation. Specific recommendations included the use of role-play, provision of science-based talking points or FAQs, and empathy for donors and staff. CONCLUSION: More than the usual training may be required to help BCO staff feel prepared to educate the public about changes to MSM-related deferrals and communicate effectively with donors about potentially deferrable behavior. Overall, these findings suggest that before future policy changes, BCO staff's opinions about and role in implementing new donor eligibility screening procedures merit consideration.

Impact of the Dapivirine Vaginal Ring on Sexual Experiences and Intimate Partnerships of Women in an HIV Prevention Clinical Trial: Managing Ring Detection and Hot Sex.

Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants' sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners' interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners' discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves.

Adherence and Acceptability of a Multidrug Vaginal Ring for HIV Prevention in a Phase I Study in the United States.

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.

Negotiating the use of female-initiated HIV prevention methods in a context of gender-based violence: the narrative of rape.

Female-initiated methods of HIV prevention are needed to address barriers to HIV prevention rooted in gender inequalities. Understanding the sociocultural context of pre-exposure prophylaxis (PrEP) trials, including gender-based violence, is thus critical. MTN-003C (VOICE-C), a qualitative sub-study of the larger MTN-003 (VOICE) trial, examined sociocultural barriers and facilitators to PrEP amongst women in Johannesburg. We conducted focus-group discussions, in-depth interviews and ethnographic interviews with 102 trial participants, 22 male partners, 17 community advisory board members and 23 community stakeholders. We analysed how discussions of rape are emblematic of the gendered context in which HIV risk occurs. Rape emerged spontaneously in half of discussions with community advisory board members, two-thirds with stakeholders and among one-fifth of interviews/discussions with trial participants. Rape was used to reframe HIV risk as external to women's or partner's behaviour and to justify the importance of PrEP. Our research illustrates how women, in contexts of high levels of sexual violence, may use existing gender inequalities to negotiate PrEP use. This suggests that future interventions should simultaneously address harmful gender attitudes, as well as equip women with alternative means to negotiate product use, in order to more effectively empower women to protect themselves from HIV.

Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 Trial.

The VOICE Adherence Strengthening Program (VASP) was implemented in May 2011 to improve adherence counseling in VOICE (MTN-003), a multisite placebo-controlled trial of daily oral or vaginal tenofovir-based Pre-Exposure Prophylaxis (PrEP). Anonymous baseline (N = 82) and final follow-up (N = 75) surveys were administered to counselors and pharmacists at 15 VOICE sites, and baseline (N = 18) and final (N = 26) qualitative in-depth interviews were conducted with purposively selected counseling staff at 13 VOICE sites. Qualitative interviews with VOICE participants (N = 38) were also analyzed for segments related to counseling. Behavioral and biological measures of product use collected in the 6 months prior to VASP implementation were compared to those collected during the 6 months following implementation. Results show that the majority of staff preferred VASP and thought that participants preferred VASP over the previous education and counseling strategy, although there was no evidence to suggest that participants noticed modifications in the counseling approach. No meaningful changes were observed in pre/post levels of reported use or drug detection. Interpretation of results is complicated by mid-trial implementation of VASP and its proximity to early closure of oral and vaginal tenofovir study arms because of futility.

Male Partner Influence on Women's HIV Prevention Trial Participation and Use of Pre-exposure Prophylaxis: the Importance of "Understanding".

There is widespread evidence that male partners influence women's ability and willingness to join HIV prevention trials and to use female-controlled prevention strategies such as microbicide gels. VOICE-C was an ancillary study to the Microbicide Trials Network's VOICE trial at the Johannesburg site that explored social and structural factors influencing women's use of study tablets and vaginal gel. Qualitative data were analyzed from 102 randomly-selected VOICE participants interviewed through in-depth interviews (IDI, n = 41); ethnographic interviews (n = 21) or focus group discussions (FGD, n = 40) and 22 male partners interviewed in 14 IDI and 2 FGD. Male partners' "understanding" pervaded as a central explanation for how male partners directly and indirectly influenced their female partners' trial participation and product use, irrespective of assignment to the gel or tablet study groups. The meaning behind "understanding" in this context was described by both men and women in two important and complementary ways: (1) "comprehension" of the study purpose including biological properties or effects of the products, and (2) "support/agreeability" for female partners being study participants or using products. During analysis a third dimension of "understanding" emerged as men's acceptance of larger shifts in gender roles and relationship power, and the potential implications of women's increased access to biomedical knowledge, services and prevention methods. Despite displays of some female agency to negotiate and use HIV prevention methods, male partners still have a critical influence on women's ability and willingness to do so. Efforts to increase their understanding of research goals, study design and products' mechanisms of action could ameliorate distrust, empower men to serve as product advocates, adherence buddies, and foster greater adherence support for women in situations where it is needed. Strategies to address gender norms and the broader implications these have for female-initiated HIV prevention should likewise be integrated into future research and program activities.

Trust - that's a big one: intimate partnership values among urban Latino youth.

Romantic relationships play a central role in young people's social development and sexual health. This paper examines romantic relationship ideals valued by urban Latino youth in San Francisco and their experiences in achieving their ideals in their current relationship. We draw on in-depth interviews with 33 young men and women aged 16-22 years in San Francisco, California. In spite of, or perhaps related to, the prevailing perception that their peers were unfaithful in their relationships, young people in this study identified trust as one of the most important characteristics of a romantic relationship. Trust was related not only to fidelity, but also vulnerability and emotional intimacy. Understanding valued relationship ideals and factors that facilitate and impede their attainment is critical in promoting healthy relationships.

Alcohol use patterns among postpartum women.

While much attention has been paid to women's drinking during pregnancy, few studies address a woman's drinking once she has given birth, which presents potential dangers to herself and her child. This time of transition can be extremely stressful, potentially leading to problem drinking. On the other hand, this new role and change in lifestyle may be protective against alcohol use and abuse. We used the California Women's Health Survey (CWHS), a randomized sample of adult women in California, to compare new mothers' drinking behaviors to other women. In order to obtain a large enough sample to observe trends in subpopulations, we combined CWHS data from years 1997-2008 (n = 28,537 women aged 18-48). We used logistic regression to determine the individual-level characteristics that best predicted the outcomes postpartum and to compare new mothers (those with a child in the household <1 year and pregnant in the last 5 years) to other women for any alcohol use, heavy episodic drinking and number of days of alcohol use. New mothers were significantly less likely to engage in all behavior outcomes after adjustment for race/ethnicity, income, employment, education, age, and marital status, though new mothers who are not married and those in higher income brackets were identified as groups at higher risk of drinking. Although new motherhood could prove to be a risk factor for some women, we found that being a new mother is protective against all measures of drinking.

Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women.

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.

Missed opportunities to prevent HIV infections among pre-exposure prophylaxis users: a population-based mixed methods study, San Francisco, United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in-depth interviews with people who HIV seroconverted after using PrEP. METHODS: We identified individuals who initiated PrEP in an integrated safety-net public health system and performed in-depth chart review to determine person-time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention's Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in-depth interviews with those who seroconverted. RESULTS: Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person-years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5-fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on-demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP's benefit versus self-perceived risk; and entering a primary partnership. The individual who developed HIV using on-demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing. CONCLUSIONS: HIV incidence during gaps in PrEP use was nearly eight-fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non-daily PrEP may require additional education and support in the United States.

Perceptions of the "Fabric" - An exploratory study of a novel multi-purpose technology among women in Sub Saharan Africa.

BACKGROUND: HIV and pregnancy prevention are dual health priorities for women, and particularly in sub-Saharan Africa. Drug-eluting fibers offer a dosage form that combines HIV prevention and contraception, but early understanding of end-user perspectives is critical to avoid misalignment between products being developed and preferred product attributes. METHODS: Focus group discussions (FGDs) were conducted in South Africa, Uganda and Zimbabwe, among 55 women who had used vaginal products in previous trials. Participants were given the opportunity to feel a sample of electrospun nanofiber (the fabric), see how it dissolves, and give feedback on shape, size and other attributes. Women were also asked to compare the fabric to vaginal gel and film. RESULTS: Three key themes regarding the acceptability of the fabric emerged: 1) look and feel of the product undissolved vs. undissolved, 2) expected effect on sex, and 3) convenience and ease of use. Upon being presented with the fabric, women were initially distrustful, seeing it as undesirable for vaginal insertion. Women generally approved of the product once they saw it dissolve. However, they stressed the importance of the product not interfering with sex by altering the vaginal environment. Women also reacted favorably to the perceived convenience of the fabric, particularly with regards to storage and transport, perceived ease of insertion and use, and dosing regimen. CONCLUSION: Multipurpose prevention technologies, and nanofibers in particular, should be developed with an eye to minimizing impact on sex while maximizing convenience, and presented in such a way as to emphasize non-abrasiveness and ease of dissolution.

Reasons for nonadherence to the dapivirine vaginal ring: narrative explanations of objective drug-level results.

OBJECTIVE(S): MTN-020/ASPIRE trial and IPM-027/Ring Study recently proved the dapivirine vaginal ring was safe and effective with consistent use. To optimize the ring's impact, the barriers and facilitators to ring adherence must be understood and addressed. METHODS: Former ASPIRE participants were stratified by age group (18-21; 22-45) and randomly selected at seven sites in Malawi, South Africa, Uganda and Zimbabwe, 12-17 months after trial exit. Using in-depth interviews or focus group discussions, ring use barriers were explored using structured guides and visual tools including individual-level depictions of dapivirine levels detected in plasma and returned rings. RESULTS: A total of 187 were enrolled; 37% were 18-21 years when they began ASPIRE. Most (75%) had drug-level results, suggesting inconsistent ring use throughout ASPIRE. Participants viewed themselves as adherent, while simultaneously describing regular instances and reasons for ring removal (e.g. for sex or menses). Less adherent women reported fears that partners would oppose the ring or feel it during sex. High adherers expressed altruistic motivations for ring use. Women of all ages attributed young women's nonadherence to their tendency to be less 'serious' about the future, HIV prevention and the study; motivated predominantly by benefits; more fearful of fertility-related consequences; and to having less relationship control. CONCLUSION: When presented with objective adherence data, participants provided reasons for intermittent ring use, while simultaneously portraying themselves as consistent ring users. Further research is needed to understand how women could use the ring in a way that fits into the context of their relationships and their lives while still conferring adequate HIV prophylaxis.

Acceptability and use of a dapivirine vaginal ring in a phase III trial.

BACKGROUND: The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. METHOD: Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. RESULTS: We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. CONCLUSION: It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden.

Disclosure of pharmacokinetic drug results to understand nonadherence.

OBJECTIVES: In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. METHODS: We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. RESULTS: We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. CONCLUSION: Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Perspectives on use of oral and vaginal antiretrovirals for HIV prevention: the VOICE-C qualitative study in Johannesburg, South Africa.

INTRODUCTION: Antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) is a promising new HIV prevention strategy. However, variable levels of adherence have yielded mixed results across several PrEP trials and populations. It is not clear how taking ARV - traditionally used for HIV treatment - is perceived and how that perception may affect the use of these products as preventives. We explored the views and experiences of VOICE participants, their male partners and community members regarding the use of ARV as PrEP in the VOICE trial and the implications of these shared meanings for adherence. METHODS: VOICE-C was a qualitative ancillary study conducted at the Johannesburg site of VOICE, a multisite, double-blind, placebo-controlled randomised trial testing tenofovir gel, oral tenofovir and oral Truvada for HIV PrEP. We interviewed 102 randomly selected female VOICE participants, 22 male partners and 40 community members through in-depth interviews, serial ethnography, or focus group discussions. All interviews were audiotaped, transcribed, translated and coded thematically for analysis. RESULTS: The concept of ARV for prevention was understood to varying degrees across all study groups. A majority of VOICE participants understood that the products contained ARV, more so for the tablets than for the gel. Although participants knew they were HIV negative, ARV was associated with illness. Male partners and community members echoed these sentiments, highlighting confusion between treatment and prevention. Concerned that they would be mistakenly identified as HIV positive, VOICE participants often concealed use of or hid their study products. This occasionally led to relationship conflicts or early trial termination. HIV stigma and its association with ARV, especially the tablets, was articulated in rumour and gossip in the community, the workplace and the household. Although ARV were recognised as potent and beneficial medications, transforming the AIDS body from sickness to health, they were regarded as potentially harmful for those uninfected. CONCLUSIONS: VOICE participants and others in the trial community struggled to conceptualise the idea of using ARV for prevention. This possibly influenced willingness to adopt ARV-based prevention in the VOICE clinical trial. Greater investments should be made to increase community understanding of ARV for prevention and to mitigate pervasive HIV stigma.

Women's experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa.

BACKGROUND: In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE. METHODS: In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis. RESULTS: Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use. CONCLUSIONS: Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and experiences with investigational products. Whether these impacted women's behaviors and may have contributed to ineffective trial results warrants further investigation.