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Data on challenges with pre-exposure prophylaxis (PrEP) uptake and adherence among Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are limited. In this mixed-methods sequential explanatory design study, our quantitative phase followed 157 at-risk, HIV-negative GBMSM who accepted PrEP and enrolled in a cohort with 12-month follow-up. Stored dried blood spots collected at two intervals were batch tested for tenofovir diphosphate (TFV-DP) concentrations at study end. Despite high self-reported adherence, only 14.6% of individuals had protective TFV-DP levels at any visit. Protective TFV-DP levels were positively associated with injection drug use and a self-assessed moderate risk of acquiring HIV, and negatively associated with time since enrolment. In our subsequent qualitative phase, an intensive workshop was conducted with the GBMSM community to identify barriers and facilitators to PrEP uptake and adherence. These data revealed numerous challenges with traditional PrEP programs that must be addressed through community collaborations.

Antiretroviral therapy (ART) adherence is suboptimal among gay, bisexual, and other men who have sex with men (GBMSM). Online interventions that incorporate social support represent new opportunities to improve adherence. This study focused on how social support was provided and sought within a technology-based ART adherence intervention. We coded and analyzed 1,751 messages. Within the social support messages, half of the time participants sought social support and half of the time they provided social support. Emotional and informational support were the most frequently exchanged forms. The most frequent topic that participants sought support around was interpersonal relationships (29%), followed by HIV care and treatment (28%). Similarly, 31% and 27% of messages in which participants provided support was related to HIV treatment and care and interpersonal relationships, respectively. HIV treatment and care issues most salient were ART adherence, lab results and upcoming tests, ART side effects, changes in ART regimens, and relationships with healthcare providers. Participants used the messaging feature in this intervention to spontaneously discuss and exchange support around HIV treatment and care. This analysis provided an opportunity to understand how participants informally interact with one another, how they seek and provide social support online, and their salient personal issues.

In trials of oral HIV pre-exposure prophylaxis (PrEP), multiple approaches have been used to measure adherence, including self-report, pill counts, electronic dose monitoring devices, and biological measures such as drug levels in plasma, peripheral blood mononuclear cells, hair, and/or dried blood spots. No one of these measures is ideal and each has strengths and weaknesses. However, accurate estimates of adherence to oral PrEP are important as drug efficacy is closely tied to adherence, and secondary analyses of trial data within identified adherent/non-adherent subgroups may yield important insights into real-world drug effectiveness. We develop a statistical approach to combining multiple measures of adherence and show in simulated data that the proposed method provides a more accurate measure of true adherence than self-report. We then apply the method to estimate adherence in the ADAPT study (HPTN 067) in South African women.

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). We measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 49-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study’s active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.

Little information is known about the cisgender women who seek and initiate pre-exposure prophylaxis (PrEP) for HIV prevention in the United States. Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week single-arm open-label demonstration study of daily oral tenofovir disoproxil fumaratel emtricitabine (TDF/FTC) in cisgender women ≥ 18 years old at risk for HIV. Participants were surveyed at screening and enrollment about sociodemographics, HIV risk perception and behaviors, and PrEP perspectives and aggregated into three risk groups according to HIV sexual risk behavior: being in a serodiscordant partnership (SD), engaging in sex work (SW), and having partners with unknown HIV status at risk for HIV (UP). One hundred sixty-seven women presented for screening with n = 31 screen failures. Of the 162 women completing enrollment, mean age was 40 (standard deviation 11), with 41% non-Hispanic Black, 22% non-Hispanic White, and 19% Latina. Compared with those who screened ineligible, enrolled participants were more likely to have heard of PrEP, had higher HIV risk perception, and reported higher perceived PrEP efficacy. Sixty-four women (47%) were categorized as SD, 21 (15%) as SW, and 51 (38%) as UP. The SW were more likely to report higher levels of drinking and drug use (p = 0.002) and history of intimate partner violence in the past year (p

A community health worker (CHW) model can promote HIV prevention and treatment behaviors, especially in highly mobile populations. In a fishing community in Rakai, Uganda, the Rakai Health Sciences Program implemented a CHW HIV intervention called Health Scouts. The situated Information, Motivation, and Behavioral Skills (sIMB) framework informed the design and a qualitative evaluation of the intervention. We interviewed 51 intervention clients and coded transcripts informed by sIMB framework dimensions. Clients reported that Health Scouts provided information about HIV prevention and treatment behaviors and helped them manage personal and social motivations to carry out health-promoting behavior. Prominent barriers which moved clients away from behavior change included daily pill burdens, anticipated stigma, serostatus disclosure, substance use at social gatherings, and anticipated reactions of partners. Our study adds to the evidence establishing CHWs as facilitators of behavior change, positioned to offer supportive encouragement and navigate contextualized circumstances.

Gay and bisexual male youth in Kenya experience human rights violations, including pervasive stigma and discrimination, and these oppressive forces are associated with elevated rates of mental health concerns. Despite these challenges, many gay and bisexual male youth in Kenya are thriving during this critical developmental period. This study explored intrapersonal processes that gay and bisexual male youth in Kisumu, Kenya, highlight as important to developing, and demonstrating resilience in the face of adversity. We conducted qualitative in-depth interviews (IDIs) with 40 gay and bisexual male youth, ages 20–30 (mean = 26.4), and an additional 20 IDIs with gay and bisexual men, ages 22–45 (mean = 26.6), who were working as peer educators (total n = 60), all in Kisumu, Kenya. A total of nine primary themes emerged which describe various intrapersonal resilience processes enacted by gay and bisexual male youth, including sexual identity acceptance, self-confidence, self-love, religious/spiritual affirmation, adaptive coping, successful navigation, legal rights awareness, economic stability, and advocacy satisfaction. These data demonstrate the range of positive personal processes that promote mental health and wellbeing among gay and bisexual male youth in Kenya. We discuss implications of these findings for community-based interventions, and call for a research paradigm shift away from deficits and toward resilience.

A sizable portion of youth (ages 13–24) living with HIV in the United States have unsuppressed viral load. The AIDS Interventions (ATN) 152 study [evaluating the Triggered Escalating Real-Time Adherence (TERA) intervention] baseline data were examined to identify correlates of high viremia (>5000 copies/mL) and self-reported adherence, which can help in planning of differentiated services for viremic youth. Depression, HIV-stigma, and cannabis use were common in this sample of 87 youth. Almost half (48%) had high viremia, which associated with enacted stigma, moderate- to high-risk alcohol use, mental health diagnosis, and age ≥21. Self-reported adherence was related to viral load and associated with mental and physical health functioning, depression, social support, self-confident decision-making, total and internalized stigma, adherence motivation, and report of a missed a care visit in the past 6 months. Mental health emerged as a common correlate of viral load and adherence. Clinical Trial Registration number: NCT03292432.

Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention modality when taken as recommended. Women in sub-Saharan Africa may have adherence challenges that remain undisclosed to providers. Real-time measures that identify non-adherence can allow for immediate exploration of adherence challenges, counseling and interventions. We conducted a formative qualitative study in Kenya to explore oral PrEP experiences and reactions to a point-of-care urine test (UT) identifying recent (past 4 days) non-adherence to tenofovir-based PrEP among female PrEP users (25 in-depth interviews; 4 focus groups) and health care provider (10 key informant interviews). Findings indicate that use of the UT would be highly feasible in the context of regular PrEP care, largely acceptable to clients and providers, and could improve adherence. Clients emphasized the need for transparent client-centered strategies in delivering results. This formative study informs the development of tools to implement this point-of-care UT in future interventional studies and clinical settings.

Introduction To guide future preexposure prophylaxis (PrEP) implementation for women who inject drugs (WWID), a population increasingly represented in new HIV cases in the United States, we present results from a demonstration project integrated within a syringe services program (SSP) in Philadelphia, PA. Methods WWID ≥18 years were educated about and offered 24 weeks of daily PrEP. Participants completed surveys and clinical assessments at baseline and at weeks 1, 3, 12, and 24. We used descriptive statistics to estimate feasibility/acceptability, engagement in the care cascade, HIV/sexually transmitted diseases (STI) and pregnancy, issues of safety/tolerability, and preferences/satisfaction with PrEP services. Multivariable logistic regression with generalized estimating equations was used to identify factors associated with PrEP uptake and retention. Results We recruited 136 WWID. Of those, 95 were included in the final sample, and 63 accepted a PrEP prescription at week 1. Uptake was associated with greater baseline frequency of SSP access [adjusted odds ratio (aOR) = 1.85; 95% confidence interval (CI): 1.24 to 2.77], inconsistent condom use (aOR = 3.38; 95% CI: 1.07 to 10.7), and experiencing sexual assault (aOR = 5.89; 95% CI: 1.02, 33.9). Of these 95, 42 (44.2%) were retained at week 24. Retention was higher among women who reported more frequent baseline SSP access (aOR = 1.46; 95% CI: 1.04 to 2.24). Self-reported adherence was high but discordant with urine-based quantification of tenofovir. Baseline STI prevalence was 17.9%; there were 2 HIV seroconversions and 1 pregnancy. Safety/tolerability issues were uncommon, and acceptability/satisfaction was high. Conclusions Integrating PrEP with SSP services is feasible and acceptable for WWID. This suggests that daily PrEP is a viable prevention tool for this vulnerable population.

Background Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW). Methods Directly observed PrEP was administered for 12 weeks in a pregnancy (14–24 weeks’ gestation, n = 20) and postpartum (6–12 weeks postpartum, n = 20) group of AGYW aged 16–24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography–tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. Results Median age was 20 (IQR, 19–22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7–12) days in pregnancy and 17 (14–21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691–1166) in pregnancy versus 1406 fmol/punch (1053–1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667–1105) in pregnancy versus 1438 fmol/punch (1178–1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. Conclusions TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women. Clinical Trials Registration NCT03386578, Concentrations of tenofovir diphosphate in dried blood spots were approximately one-third lower during pregnancy than postpartum after 12 weeks of directly observed dosing among African adolescent girls and young women on daily pre-exposure prophylaxis. We recommend population-specific benchmarks for adherence support.

Youth living with HIV (YLWH) in the US have low rates of viral suppression (VS). In a prospective randomized clinical trial (ATN152) that enrolled 89 YLWH on antiretroviral therapy (ART) with detectable viral load, we evaluated a 12 week triggered escalating real-time adherence (TERA) intervention with remote coaching, electronic dose monitoring (EDM), and outreach for missed/delayed doses compared to standard of care (SOC). Median [Q1, Q3] percent days with EDM opening was higher in TERA (72% (47%, 89%)) versus SOC (41% (21%, 59%); p 0.001) and incidence of numbers of 7 day gaps between openings were lower (TERA to SOC ratio: 0.40; 95% CI 0.30, 0.53; p 0.001). There were no differences in VS at week 12 (TERA 35%; 95% CI 21%, 51% versus SOC 36%; 95% CI 22%, 51%; p 0.99) or later time-points. The intervention improved adherence but not VS in heavily ART-experienced YLWH. Remote coaching more closely tailored to the unique dosing patterns and duration of need for youth struggling to reach VS warrants further investigation.

Structural stigma shapes men who have sex with men’s (MSM’s) mental health and sexual behaviours. The aim of this study was to examine how stigmatizing policies interact with downstream anxiety/depression and sexual behaviours to structurally pattern HIV disparities among European MSM. We conducted a secondary data analysis of the European Men-who-have-sex-with-men Internet Survey (EMIS) from 2017. We included a total of 98,600 participants living in 39 European countries. We used the Rainbow Index, a score given to countries based on their sexual and gender minority policies as the predictor of HIV diagnosis. We conducted adjusted random intercept and slope multi-level logistic regressions. In adjusted models, higher Rainbow Index scores was associated with lower predictive probabilities of diagnosed HIV, regardless of the number of condomless intercourse partners. The predictive probability of HIV diagnosis was also lower, regardless of severity of anxiety/depression, where the Rainbow Index score was better. Country-level policies interact with downstream sexual behaviours and anxiety/depression to structurally influence HIV diagnosis among MSM in Europe.

Stigma regarding HIV pre-exposure prophylaxis (PrEP) is commonly implicated as a factor limiting the scale-up of this highly effective HIV prevention modality. To quantify and characterize PrEP stigma, we developed and validated a brief HIV PrEP Stigma Scale (HPSS) among a group of 279 men who have sex with men (MSM). Scale development was informed by a theoretical model to enhance content validity. We assessed two scale versions, Semantic Differential and Likert, randomizing the order in which scales were presented to participants. Both scales demonstrated high internal consistency. The Likert scale had substantially better construct validity and was selected as the preferred option. Scale scores demonstrated construct validity through association with constructs of interest: healthcare distrust, HIV knowledge, perceived proportion of friends/partners on PrEP, perceived community evaluation of PrEP, and perceived effectiveness of PrEP. The scale accounted for 25% of the total variance in reported willingness to be on PrEP, indicating the substantial role PrEP stigma may have on decisions to initiate PrEP. Given increased efforts to roll-out PrEP, having a valid tool to determine the level and types of PrEP stigma in individuals, groups, and communities can help direct implementation plans, identify goals for stigma reduction, and monitor progress over time. Electronic supplementary material The online version of this article (10.1007/s10461-020-02820-6) contains supplementary material, which is available to authorized users.

Self-reported HIV risk perception and behaviors are used in a variety of settings for diverse purposes, such as HIV prevention program planning and screening. Careful consideration of how youth in high HIV prevalence areas interpret these kinds of questions warrants attention. The Cognitive Interviewing Project (CIP) conducted cognitive interviews on common risk survey items with 30 cis-female and 20 MSM youth (18 to 24), who had recent sex with a male partner, in Cape Town and Vulindlela, South Africa. Results identified a number of potential issues including (1) confusing text; (2) mismatches of terms with local usage; (3) confusion with items requiring self-tailoring; (4) presentation concerns limiting selection of full range of answers; and (5) challenges reporting on information dependent on partner (eg., HIV risk, HIV status of partner). Self-report Items used to identify those at elevated risk for HIV should be evaluated with local populations to optimize shared understanding.

BackgroundHIV- and MSM-related stigma are well documented as common for Chinese men who have sex with men (MSM) living with HIV, yet there is sparse literature on intimate partner violence (IPV) and its relationship with stigma in this vulnerable population. To evaluate the association between HIV-stigma and stigma related to homosexuality and IPV among newly HIV-diagnosed MSM in China.MethodsData were collected in the baseline survey among newly HIV-diagnosed Chinese MSM in a randomized clinical trial via face-to-face interviews. Univariate logistic and multivariate logistic regression analyses were performed to assess the associations between IPV and HIV- and MSM-related stigma.ResultsOf 367 newly HIV-diagnosed Chinese MSM, 23.7% experienced any IPV, including 16.6% physical, 7.4% psychological and 5.2% sexual IPV. Positive associations were found between HIV- and MSM-related stigma and IPV. Men with high HIV-related stigma (score ≥ 27) were 1.67 times as likely to experience any IPV as those with low stigma (adjusted odds ratio [AOR]: 1.67, 95% confidence interval [CI]: 1.02–2.76). Men with high MSM-related stigma (score ≥ 6) were 1.99 times as likely to experience any IPV as those with low stigma (AOR: 1.99, 95% CI: 1.18–3.36).ConclusionsHIV- and MSM-related stigmas was positively associated with IPV experiences among newly diagnosed MSM in China. The manner in which stigma may exacerbate IPV, and/or the influence of IPV on worsening stigma should be further evaluated. The high prevalence of IPV and stigma in this population suggests that interventions should be taken to reduce stigma and prevent this risky behavior among MSM.

We piloted the combined effectiveness of point-of-care viral load monitoring plus motivational enhanced adherence counseling (intervention) compared with routine care (control) in women identified at risk of virologic failure in the PROMOTE study in Zimbabwe. In an unblinded randomized study, consenting women with last viral load ≥200 copies/ml and/or pill count outside 90–110% range were randomized 1 : 1 to receive the intervention or continue routine care, comprising laboratory-based VL monitoring and standard EAC, from trained nurses and counsellors. Viral load was measured 0, 3, 6, and 12 months after enrolment. We compared viral suppression p value = 0.248). At month 6 post study entry (primary endpont), 64% of the women retained in care were virally suppressed, 54% intervention vs. 76% control arm ( p value = 0.124). At month12 post study entry (secondary endpoint), 69% of the women retained in care were virally suppressed, 67% intervention vs. 71% control arm women ( p value = 0.739). More intervention women completed all scheduled sessions by month 6. Control group women were more likely to be virally suppressed at both timepoints. Only 25% had treatment switch by 12 months. Despite intense adherence support and viral load monitoring, sustained viral suppression remained elusive in women identified at risk of viral failure. These findings highlight the continued need for effective adherence intervention for women with unsuppressed HIV viral loads, efficient treatment switch strategies, as well as drug level monitoring.

Gay and bisexual men and other men who have sex with men (GBMSM) experience many sexual orientation-related stressors that negatively influence physical and mental health, making it imperative to understand their experiences of resilience-promoting resources such as social support. We utilized qualitative and participatory methodologies to examine sources of social support and types of social support received by GBMSM in Western Kenya through in-depth interviews with 60 GBMSM, including both peer educators and community members. GBMSM received emotional, informational, and instrumental support from six different relationship types: friends and peer groups, family of origin, sexual and romantic partners, healthcare providers, peer educators, and other people including work colleagues and police officers. A key finding from this study is the centrality of sexuality-specific support across all sources and types of support. Implications for clinics and LGBTQ organizations, policy, and future research are discussed.

Background Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women. Methods Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence. Results From June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections. Conclusion Adequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women.

Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes.This is a prospective cohort study conducted in KwaZulu-Natal, South Africa.Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance-associated variants.From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2-19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P0.001) but correlated (r2 = 0.68, P0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance-associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome.Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.

A correction to this paper has been published: https://doi.org/10.1007/s10461-022-03884-2

IntroductionTo realise the expected gains from prevention of mother-to-child HIV transmission initiatives, adherence to preventative and therapeutic antiretroviral regimens is critical and interventions deployable in busy programmatic settings with a high HIV burden are needed. Based on formative research, we developed an approach that integrates patient-centred counselling and engagement of an adherence supporter for pregnant and breastfeeding women initiating HIV treatment (ie, antiretroviral therapy (ART)) or biomedical HIV prevention (ie, pre-exposure prophylaxis (PrEP)).MethodsTonse Pamodzi 2 is a pilot study designed to provide acceptability, fidelity and clinical outcomes data on a set of behavioural interventions for adherence support. The study comprises two parallel randomised trials, enrolling HIV-positive pregnant women initiating ART (Trial 1, n=100) and HIV-negative pregnant women with risk of HIV acquisition and willing to initiate PrEP (Trial 2, n=200). Within each trial, participants are randomised 1:1 to either the intervention or control group. The Tonse Pamodzi adherence intervention comprises patient-centred counselling (adapted Integrated Next Step Counseling(iNSC)) and external adherence support tailored to the clinical context (ie, for ART or PrEP). Participants randomly assigned to the control group receive standard counselling based on local HIV guidelines. Participants are followed for 6 months. To assess intervention acceptability, we will employ a mixed method approach to describe participant engagement, satisfaction, and discussion content. We will audit and score recorded counselling sessions to evaluate the implementation fidelity of iNSC sessions. We will also assess clinical outcomes at 3 and 6 months for both Trial 1 (retention in care and viral suppression of HIV) and Trial 2 (retention in care, and plasma and intracellular tenofovir drug concentrations).Ethics and disseminationThe study protocol was approved by the Malawi National Health Science Research Committee (19/05/2334) and the University of North Carolina at Chapel Hill Institutional Review Board (19-1060).Trial registration numberNCT04330989.

BACKGROUND: We identified correlates of sex-related pre-exposure prophylaxis (PrEP) adherence in HPTN067/ADAPT, a phase 2, open-label feasibility study of daily and non-daily regimens of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based PrEP, among Thai men who have sex with men (MSM), and transgender women (TGW), Bangkok. METHODS: Participants were randomly assigned to one of three self-administered dosing regimens for 24 weeks: daily, time-driven, or event-driven. Demographic and behavioral information was obtained at screening. Pill-container opening was recorded with electronic dose monitoring, and self-reported information on PrEP use, sex events, and substance use were obtained during weekly interviews to confirm dose data. Sex-related PrEP adherence was calculated the proportion of sex events covered by PrEP use (at least one tablet taken within four days before sex and at least one tablet taken within 24 hours after sex) to total sex events. We used multivariate modeling with sex event as the unit of analysis to evaluate correlates associated with sex-related PrEP adherence. RESULTS: Among 178 MSM and TGW, sex-related PrEP adherence was similar in the daily and time-driven arms (p=0.79), both significantly greater than the event-driven arm (p=0.02 compared to daily). Sex-related PrEP adherence by those reporting stimulant use (74.2%) was similar to those reporting other non-alcohol drug use (76.3%, p=0.80), but lower than those reporting no substance use (84.6%, p=0.04). In a multivariable model, randomization to the event-driven arm, a higher pre-study number of reported sex events, and use of stimulant drugs were associated with significantly lower sex-related PrEP adherence. CONCLUSION: Adherence was influenced by treatment schedule and adversely impacted by non-alcoholic substance use. Regardless of these factors, Thai MSM and TGW maintained high adherence levels to oral PrEP dosing regimens and coverage of sexual exposures.

Uptake of pre-exposure prophylaxis (PrEP) has dramatically increased but remains well below the estimated number of individuals who could benefit from PrEP in the United States, and uptake remains limited among young men who have sex with men (YMSM) and MSM of color. Reasons for not adopting PrEP as a prevention strategy among those at elevated risk for HIV is an important area of inquiry that could advise efforts to better position PrEP as an active part of prevention programs. As part of a mixed methods study investigating experiences with repeat HIV testing, we identified main themes emerging from in-depth interview data pertaining to reasons why YMSM report not using PrEP, among YMSM with frequent access to HIV testing services. Themes from 14 in-depth interviews with predominantly Latino MSM for not using PrEP included perceived burden of daily dosing, feeling that risk was not high enough to warrant PrEP, and beliefs that PrEP would have severe adverse events affecting the kidneys and bones. Less prominent but noteworthy themes included stigma as a PrEP user, social or provider influence on decisions not to use PrEP, and preference for current prevention strategy. No differences in PrEP discourse were noted across those at different levels of HIV risk. Results suggest that efforts are needed to engage communities and individuals around PrEP-related education, facilitate risk evaluation, and reduce PrEP stigma. New formulations and nondaily regimens may also be of particular interest to YMSM who may perceive daily PrEP regimens as highly burdensome.

We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg.Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence.Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(β) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(β) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001].Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

The HPTN 067/ADAPT Study evaluated the feasibility, acceptability and patterns of adherence and coverage for three randomly assigned oral FTC/TDF pre-exposure prophylaxis (PrEP) dosing regimens to prevent HIV infection: daily, time-driven (twice a week with a post-sex dose), and event-driven (pre/post-sex dosing). Using qualitative methods, we explored facilitators and barriers for each regimen among a subset of men who have sex with men (MSM) participants in Bangkok, Thailand. Between August 2013 and March 2014, 32 (of 179) HPTN 067/ADAPT participants joined in six focus group discussions, and six attended key-informant interviews – two per each study regimen. Facilitators of PrEP adherence included use of strategies to have PrEP available when needed and constructing convenient dosing regimens, simplicity in regimen requirements with recognition that more complex regimens may take some time to master, ability to plan for sex (non-daily regimens), receipt of social and technology support, ability to use a PrEP regimen that best matches to one’s own patterns of sex, and experiences with PrEP as a part of health and well-being. Challenges to PrEP adherence included perceptions of no or low HIV risk, difficulties following regimens when drinking (intoxicated), concerns about short or long-term side-effects of PrEP, experience of HIV stigma (fears of being misidentified as HIV positive), inability to forecast sex events for non-daily regimens, and affordability of PrEP outside of study context influencing uptake and use in the community. Preferences for regimens varied, suggesting that multiple PrEP effective regimen options (daily and non-daily) should be available to fit those with different needs.

Author(s): Velloza, Jennifer; Bacchetti, Peter; Hendrix, Craig W; Murnane, Pamela; Hughes, James P; Li, Maoji; Curlin, Marcel E; Holtz, Timothy H; Mannheimer, Sharon; Marzinke, Mark A; Amico, K Rivet; Liu, Albert; Piwowar-Manning, Estelle; Eshleman, Susan H; Dye, Bonnie J; Gandhi, Monica; Grant, Robert M; HPTN 067/ADAPT Study Team | Abstract: BackgroundThe effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate-based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence.SettingWe analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S.MethodsAfter a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations.ResultsAmong 350 participants (median age: 31 years, interquartile range: 25-38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non-daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits.ConclusionsIn HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.

Background Prior to implementing a pre-exposure prophylaxis (PrEP) demonstration study, we sought to explore cisgender women’s experiences with HIV prevention, PrEP knowledge and attitudes, and anticipated barriers and facilitators for PrEP uptake and adherence in Southern California. Methods Three focus groups were held with cisgender women of mixed HIV serostatus in San Diego and Los Angeles between November 2015 and January 2016. Women were recruited through local testing sites, community-based organizations, and social media. Focus groups were audio-recorded and transcripts were analyzed using thematic analysis. Results Twenty-two women participated in focus groups, with median age 44 (IQR 30–53) and 6 identifying as non-Hispanic Black, 7 non-Hispanic White, 8 Latina and 1 mixed race. Despite limited prior PrEP knowledge and no PrEP experience, participants expressed interest in taking PrEP. Anticipated benefits were freedom from worry about HIV and control over sexual health; however, these were tempered by concerns including the possibility of increased HIV risk behaviors and potential side effects. Cisgender women reported potential barriers to PrEP uptake and adherence barriers, like competing priorities and poor PrEP access. Conversely, PrEP facilitators included utilizing practical tools such as phone apps and pill boxes as well as receiving encouragement from loved ones and support from other cisgender women on PrEP, women living with HIV and their medical providers. Conclusions Although PrEP awareness was low, participants recognized the importance of PrEP and ways to facilitate adherence. Exploring perspectives of cisgender women is integral to developing effective interventions to support PrEP uptake and adherence for women at elevated risk for HIV.

Author(s): Sekabira, Rogers; McGowan, Ian; Yuhas, Krista; Brand, Rhonda M; Marzinke, Mark A; Manabe, Yukari C; Frank, Ian; Eron, Joseph; Landovitz, Raphael J; Anton, Peter; Cranston, Ross D; Anderson, Peter; Mayer, Kenneth H; Amico, K Rivet; Wilkin, Timothy J; Chege, Wairimu; Kekitiinwa, Adeodata R; McCauley, Marybeth; Gulick, Roy M; Hendrix, Craig W | Abstract: ObjectiveThe objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype.DesignA substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group.MethodsPlasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug). Drug concentrations were assessed in all matrices. HIV infectivity was assessed using tissue biopsy 'explants' challenged with HIV ex vivo followed by HIV p24 measurement. Flow cytometry evaluated colorectal cell phenotype.ResultsThirty-seven CGW and 54 MSM participated. CGW's colorectal explant p24 was higher than MSM before (0.31 log10, P = 0.046), during (1.01-1.19 log10, P = 0.016) and one week after (0.61 log10, P = 0.011) study drug dosing. Pooling regimens, cervical explant p24 did not differ among visits. CGW had higher plasma maraviroc and colorectal tissue tenofovir diphosphate and lower colorectal tissue emtricitabine (all P l 0.005) compared with MSM. Each study drug's cervical tissue concentrations were more than 10-fold below paired colorectal concentrations (P l 0.001). Cell phenotype sex differences included 4% higher CD38+/CD8+ cells at baseline and 3-7% higher CD69+/CD8+ cells throughout Weeks 24-49 in CGW compared with MSM (P l 0.05).ConclusionColorectal explants in CGW demonstrated greater HIV infectivity than MSM with and without study drugs. Small differences in adherence, drug concentration and colorectal tissue flow cytometry cannot fully explain this difference.

Author(s): Felner, Jennifer K; Mittal, Maria L; Hoenigl, Martin; Amico, K Rivet; Grelotti, David J; Eanes, Alex; Hess, Kristen; Crawford, Jessica; Smith, Laramie R | Abstract: IntroductionTo end the HIV epidemic, HIV prevention and pre-exposure prophylaxis (PrEP) promotion efforts must reach young men who have sex with men (YMSM) at greatest risk for HIV. This study qualitatively explored whether common metrics used by clinicians, scientists, and public health officials to objectively assess HIV risk align with how YMSM conceptualize their risk for HIV and the factors that shape YMSM's risk perceptions.MethodsInterviews with a racially/ethnically diverse sample of HIV-negative YMSM (ages 19-24 years, 60% Latinx; n = 20) examined conceptualizations of HIV risk within the context of repeat HIV testing. Iterative, applied thematic analysis examined how participants conceptualized and constructed their HIV risk, and compared participants' descriptions of their risk with a validated quantitative assessment of HIV risk that reliably predicts HIV seroconversion in this group.ResultsObjective quantitative assessments of HIV risk poorly aligned with participants' perceived HIV risk. Participants described their current risk in relative terms (relative to past risk and relative to friends'/peers' risk) and described age/developmental stage and changes in knowledge about HIV prevention as key factors in risk changes over time. Other factors included substance use and trust/mistrust in sexual partners and scientific advances in HIV prevention (eg, U = U and PrEP). Factors that influenced participants' perceived HIV risk were similar regardless of objective risk assessment.ConclusionsQuantitative assessments of risk may poorly align with risk perception among YMSM. Although objective metrics can effectively target YMSM at greatest risk for HIV transmission, interventions to improve prevention behaviors and PrEP uptake may be more effective when tailored to bridge the disconnection between objective HIV risk assessments and YMSM's constructions of risk.

Additional file 1. Focus Group Guide.

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi (“all of us together”), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT.

BackgroundAntiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate.MethodsThis multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of

INTRODUCTION: Understanding the reasons why clients stop taking pre-exposure prophylaxis (PrEP) is critical to improving PrEP delivery and ultimately reducing HIV incidence. METHODS: We analyzed data from a programmatic evaluation conducted at the Los Angeles LGBT Center (the Center) from February-May 2018. In the evaluation, an online structured questionnaire was emailed to inactive PrEP clients. RESULTS: Of 180 survey respondents, 91 had stopped taking PrEP and 11 had never started. Most who stopped using PrEP did so for reasons spanning multiple categories. Among former PrEP users, the most common reasons for stopping were entering a monogamous relationship (43%) and side effects (40%). Ten of 11 who never started PrEP reported access barriers (e.g., cost was too high, problems with insurance). An unexpected finding was that the survey led 25% of inactive clients to re-engage with PrEP services at the Center and 15% to restart PrEP by October 2018. CONCLUSION: The findings show that improving PrEP retention may require multifaceted interventions – e.g., tailored discussions about stopping and restarting PrEP safely as HIV risk changes, ensuring consistent access to affordable PrEP, and alternative dosing strategies. An emailed survey appears to be a simple yet effective strategy to reengage some clients in PrEP care.