Emotion regulation as a potential moderator of the association between HIV stigma and nonadherence to antiretroviral therapy among youth living with HIV.

INTRODUCTION: Human immunodeficiency virus (HIV)-related stigma affects adherence to antiretroviral therapy (ART) for youth living with HIV. Emotion regulation strategies such as cognitive reappraisal (reinterpreting adversity to mitigate emotional impact) and expressive suppression (inhibiting emotion-expressive behavior activated by adversity) may moderate the HIV stigma-ART adherence relationship in this group. METHODS: Using baseline data from 208 youth living with HIV aged 15-24 years enrolled in an mHealth ART-adherence intervention, we performed modified Poisson regressions with robust variance between HIV stigma (internalized, anticipated, enacted) and ART nonadherence. We tested for multiplicative interaction via product terms between HIV stigma and emotion regulation scores, and additive interaction via relative excess risk due to interaction and attributable proportion using dichotomous HIV stigma and emotion regulation variables. RESULTS: Mean age was 21 years; ≥50% of participants were cisgender male, non-Hispanic Black, and gay-identifying; 18% reported ART nonadherence. Confounder-adjusted regressions showed positive associations between each HIV stigma variable and ART nonadherence. Internalized HIV stigma and cognitive reappraisal negatively, multiplicatively interacted (as internalized HIV stigma increased, ART nonadherence increased for those with low cognitive reappraisal). High internalized HIV stigma positively, additively interacted with low cognitive reappraisal and low expressive suppression (when high internalized HIV stigma and low levels of either emotion regulation strategy were present, ART nonadherence increased dramatically). CONCLUSION: Cognitive reappraisal and expressive suppression may protect against internalized HIV stigma's harmful association with ART nonadherence. These modifiable emotion regulation strategies may be targeted to potentially buffer the effects of internalized HIV stigma and support ART adherence for youth living with HIV.

Differentiated service delivery framework for people with multidrug-resistant tuberculosis and HIV co-infection.

INTRODUCTION: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework. METHODS: Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices (EDM) measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges. RESULTS: 283 participants were enrolled and followed through treatment completion (median 17.8 months [IQR 16.5-20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (p<0.0001) and mean weekly ART adherence from 83.9% to 26.6% (p<0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages, and identified potential stage specific interventions. CONCLUSION: A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multi-modal support for adherence across the treatment course and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages.

Motivational interviewing experiences from a community health worker-led HIV prevention and care intervention in rural Uganda: a qualitative study.

Motivational Interviewing (MI) and Community Health Workers (CHWs) are increasingly utilized in global settings to improve HIV outcomes, yet research exploring implementation strategies using MI and CHWs is lacking. We examined the experiences of CHWs and their clients in a counseling intervention which used MI-informed counseling to increase engagement in HIV prevention and treatment. This study was nested within the mLAKE cluster-randomized trial in a high HIV prevalence fishing community in rural Rakai District, Uganda. We conducted in-depth interviews with purposively-sampled CHWs (n = 8) and clients (n = 51). Transcripts were analyzed thematically to characterize CHWs' implementation of the intervention. Main themes identified included use of specific MI strategies (including evocation, guidance towards positive behavior change, active listening, and open-ended questions), and MI spirit (including collaboration, power-sharing, trust, and non-judgmental relationship building). Through these specific MI mechanisms, CHWs supported client behavior change to facilitate engagement with HIV services. This study provides evidence from a low-resource setting that CHWs with no previous experience in MI can successfully implement MI-informed counseling that is well-received by clients. CHW-led MI-informed counseling appears to be a feasible and effective approach to increase uptake of HIV prevention and care services in low-resource, HIV endemic regions.

A Patient-Centered, Combination Intervention to Support Adherence to HIV Pre-exposure Prophylaxis During Pregnancy and Breastfeeding: A Randomized Pilot Study in Malawi.

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV incidence in pregnant and breastfeeding women, but adherence is essential. METHODS: We conducted a pilot randomized trial to evaluate an intervention package to enhance antenatal and postnatal PrEP use in Lilongwe, Malawi. The intervention was based on patient-centered counseling adapted from previous PrEP studies, with the option of a participant-selected adherence supporter. Participants were locally eligible for PrEP and randomized 1:1 to intervention or standard counseling (ie, control) and followed for 6 months. Participants received the intervention package or standard counseling at enrollment, 1, 3, and 6 months. Adherence was measured through plasma and intracellular tenofovir concentrations and scored using a published algorithm. Our primary outcome was retention in care with concentrations consistent with 4-7 doses/week. RESULTS: From June to November 2020, we enrolled 200 pregnant women with the median gestational age of 26 (interquartile range: 19-33) weeks. Study retention was high at 3 months (89.5%) and 6 months (85.5%). By contrast, across the 2 time points, 32.8% of participants retained in the study had adherence scores consistent with 2-5 doses/week while 10.3% had scores consistent with daily dosing. For the composite primary end point, no substantial differences were observed between the intervention and control groups at 3 months (28.3% vs. 29.0%, probability difference: -0.7%, 95% confidence interval: -13.3%, 11.8%) or at 6 months (22.0% vs. 26.3%, probability difference: -4.3%, 95% confidence interval: -16.1%, 7.6%). CONCLUSIONS: In this randomized trial of PrEP adherence support, retention was high, but less than one-third of participants had pharmacologically confirmed adherence of ≥4 doses/week. Future research should focus on antenatal and postnatal HIV prevention needs and their alignment across the PrEP continuum, including uptake, persistence, and adherence.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): study protocol for an adaptive randomized controlled trial.

BACKGROUND: Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. METHODS: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. DISCUSSION: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support. TRIAL REGISTRATION: ClinicalTrials.gov NCT05633056. Registered on 1 December 2022.

Acceptability of a Combination Adherence Strategy to Support HIV Antiretroviral Therapy and Pre-exposure Prophylaxis Adherence During Pregnancy and Breastfeeding in Malawi.

In two parallel pilot studies, we implemented a combination adherence intervention of patient-centered counselling and adherence supporter training, tailored to support HIV treatment (i.e., antiretroviral therapy) or prevention (i.e., pre-exposure prophylaxis, or PrEP) during pregnancy and breastfeeding. Using a mixed-methods approach, we evaluated the intervention's acceptability. We investigated engagement, satisfaction, and discussion content via survey to all 151 participants assigned to the intervention arm (51 women living with HIV, 100 PrEP-eligible women without HIV). We also conducted serial in-depth interviews with a subgroup (n = 40) at enrollment, three months, and six months. In the quantitative analysis, the vast majority reported high satisfaction with intervention components and expressed desire to receive it in the future, if made available. These findings were supported in the qualitative analysis, with favorable comments about counselor engagement, intervention content and types of support received from adherence supporters. Overall, these results demonstrate high acceptability and provide support for HIV status-neutral interventions for antiretroviral adherence.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): Study protocol for an adaptive randomized controlled trial.

Background: Highly effective, short course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. Methods: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include 1) enhanced standard of care; 2) psychosocial support; 3) mHealth using cellular- enabled electronic dose monitoring; 4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will be include survival, negative TB culture, retention in care and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. Discussion: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

Mass spectrometry imaging of hair identifies daily maraviroc adherence in HPTN 069/ACTG A5305.

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). Here, 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 48-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.

Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Drugs taken during pregnancy can affect maternal and child health outcomes, but few studies have compared the safety and virological efficacy of different antiretroviral therapy (ART) regimens. We report the primary safety outcomes from enrolment up to 50 weeks post partum and a secondary virological efficacy outcome at 50 weeks post partum of three commonly used ART regimens for HIV-1. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, we enrolled pregnant women aged 18 years or older with confirmed HIV-1 infection at 14-28 weeks of gestation. Women were enrolled at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Participants were randomly assigned (1:1:1) to one of three oral regimens: dolutegravir, emtricitabine, and tenofovir alafenamide; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; or efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Up to 14 days of antepartum ART before enrolment was permitted. Women with known multiple gestation, fetal anomalies, acute significant illness, transaminases more than 2·5 times the upper limit of normal, or estimated creatinine clearance of less than 60 mL/min were excluded. Primary safety analyses were pairwise comparisons between ART regimens of the proportion of maternal and infant adverse events of grade 3 or higher up to 50 weeks post partum. Secondary efficacy analyses at 50 weeks post partum included a comparison of the proportion of women with plasma HIV-1 RNA of less than 200 copies per mL in the combined dolutegravir-containing groups versus the efavirenz-containing group. Analyses were done in the intention-to-treat population, which included all randomly assigned participants with available data. This trial was registered with ClinicalTrials.gov, NCT03048422. FINDINGS: Between Jan 19, 2018, and Feb 8, 2019, we randomly assigned 643 pregnant women to the dolutegravir, emtricitabine, and tenofovir alafenamide group (n=217), the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (n=215), and the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (n=211). At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), median CD4 count was 466 cells per µL (308-624), and median HIV-1 RNA was 903 copies per mL (152-5183). 607 (94%) women and 566 (92%) of 617 liveborn infants completed the study. Up to the week 50 post-partum visit, the estimated probability of experiencing an adverse event of grade 3 or higher was 25% in the dolutegravir, emtricitabine, and tenofovir alafenamide group; 31% in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group; and 28% in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (no significant difference between groups). Among infants, the estimated probability of experiencing at least one adverse event of grade 3 or higher by postnatal week 50 was 28% overall, with small and non-statistically significant differences between groups. By postnatal week 50, 14 infants whose mothers were in the efavirenz-containing group (7%) died, compared with six in the combined dolutegravir groups (1%). 573 (89%) women had HIV-1 RNA data available at 50 weeks post partum: 366 (96%) in the dolutegravir-containing groups and 186 (96%) in the efavirenz-containing group had HIV-1 RNA less than 200 copies per mL, with no significant difference between groups. INTERPRETATION: Safety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy. FUNDING: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Mixed Methods, Implementation Science Evaluation of a Community Health Worker Strategy for HIV Service Engagement in Uganda.

BACKGROUND: A trial found that a community health worker (CHW) strategy using "Health Scouts" improved HIV care uptake and ART coverage. To better understand outcomes and areas for improvement, we conducted an implementation science evaluation. METHODS: Using the RE-AIM framework, quantitative methods included analyses of a community-wide survey (n = 1903), CHW log books, and phone application data. Qualitative methods included in-depth interviews (n = 72) with CHWs, clients, staff, and community leaders. RESULTS: Thirteen Health Scouts logged 11,221 counseling sessions; 2532 unique clients were counseled. 95.7% (1789 of 1891) of residents reported awareness of the Health Scouts. Overall, reach (self-reported receipt of counseling) was 30.7% (580 of 1891). Unreached residents were more likely to be male and HIV seronegative ( P < 0.05). Qualitative themes included the following: (1) reach was promoted by perceived usefulness but deterred by busy client lifestyles and stigma, (2) effectiveness was enabled through good acceptability and consistency with the conceptual framework, (3) adoption was facilitated by positive impacts on HIV service engagement, and (4) implementation fidelity was initially promoted by the CHW phone application but deterred by mobility. Maintenance showed consistent counseling sessions over time. The findings suggested the strategy was fundamentally sound but had suboptimal reach. Future iterations could consider adaptations to improve reach to priority populations, testing the need for mobile health support, and additional community sensitization to reduce stigma. CONCLUSIONS: A CHW strategy to promote HIV services was implemented with moderate success in an HIV hyperendemic setting and should be considered for adoption and scale-up in other communities as part of comprehensive HIV epidemic control efforts. TRIAL REGISTRATION: ClinicalTrials.gov Trial Number NCT02556957.

Conceptualising engagement with HIV care for people on treatment: the Indicators of HIV Care and AntiRetroviral Engagement (InCARE) Framework.

BACKGROUND: As the crisis-based approach to HIV care evolves to chronic disease management, supporting ongoing engagement with HIV care is increasingly important to achieve long-term treatment success. However, 'engagement' is a complex concept and ambiguous definitions limit its evaluation. To guide engagement evaluation and development of interventions to improve HIV outcomes, we sought to identify critical, measurable dimensions of engagement with HIV care for people on treatment from a health service-delivery perspective. METHODS: We used a pragmatic, iterative approach to develop a framework, combining insights from researcher experience, a narrative literature review, framework mapping, expert stakeholder input and a formal scoping review of engagement measures. These inputs helped to refine the inclusion and definition of important elements of engagement behaviour that could be evaluated by the health system. RESULTS: The final framework presents engagement with HIV care as a dynamic behaviour that people practice rather than an individual characteristic or permanent state, so that people can be variably engaged at different points in their treatment journey. Engagement with HIV care for those on treatment is represented by three measurable dimensions: 'retention' (interaction with health services), 'adherence' (pill-taking behaviour), and 'active self-management' (ownership and self-management of care). Engagement is the product of wider contextual, health system and personal factors, and engagement in all dimensions facilitates successful treatment outcomes, such as virologic suppression and good health. While retention and adherence together may lead to treatment success at a particular point, this framework hypothesises that active self-management sustains treatment success over time. Thus, evaluation of all three core dimensions is crucial to realise the individual, societal and public health benefits of antiretroviral treatment programmes. CONCLUSIONS: This framework distils a complex concept into three core, measurable dimensions critical for the maintenance of engagement. It characterises elements that the system might assess to evaluate engagement more comprehensively at individual and programmatic levels, and suggests that active self-management is an important consideration to support lifelong optimal engagement. This framework could be helpful in practice to guide the development of more nuanced interventions that improve long-term treatment success and help maintain momentum in controlling a changing epidemic.

Adolescents Living With or at Risk for HIV: A Pooled Descriptive Analysis of Studies From the Adolescent Medicine Trials Network for HIV/AIDS Interventions.

PURPOSE: This study aims to describe the cohort of Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) research program participants and evaluate whether the ATN's recently completed 5-year cycle recruited study participants who parallel the populations most impacted by HIV in the United States. METHODS: Harmonized measures across ATN studies collected at baseline were aggregated for participants aged 13-24 years. Pooled means and proportions stratified by HIV status (at risk for or living with HIV) were calculated using unweighted averages of study-specific aggregate data. Medians were estimated using a weighted median of medians method. Public use 2019 Centers for Disease Control and Prevention surveillance data for state-level new HIV diagnoses and HIV prevalence among US youth aged 13-24 years were obtained for use as reference populations for ATN at-risk youth and youth living with HIV (YLWH), respectively. RESULTS: Data from 3,185 youth at-risk for HIV and 542 YLWH were pooled from 21 ATN study phases conducted across the United States. Among ATN studies tailored to at-risk youth, a higher proportion of participants were White and a lower proportion were Black/African American and Hispanic/Latinx compared to youth newly diagnosed with HIV in the United States in 2019. Participants in ATN studies tailored to YLWH were demographically similar to YLWH in the United States. DISCUSSION: The development of data harmonization guidelines for ATN research activities facilitated this cross-network pooled analysis. These findings suggest the ATN's YLWH are representative, but that future studies of at-risk youth should prioritize recruitment strategies to enroll more participants from African American and Hispanic/Latinx populations.

Electronic Dose Monitoring Device Patterns in Youth Living With HIV Enrolled in an Adherence Intervention Clinical Trial.

INTRODUCTION: Youth living with HIV in the US have low rates of viral suppression, in part because of challenges with antiretroviral therapy adherence. METHODS: Daily dosing in the Adolescent Medicine Trials Network for HIV/AIDS Interventions 152 study, a randomized controlled trial of a 12-week adherence intervention (triggered escalating real-time adherence intervention) for viremic youth, compared with standard of care (SOC), was measured by electronic dose monitoring (EDM) throughout 48 weeks of follow-up. EDM data collected over the first 24 weeks were used to characterize patterns of antiretroviral therapy adherence with group-based trajectory models. RESULTS: Four trajectory groups were identified among the 85 participants included in the analysis during the intervention phase of the study: (Worst) no interaction with EDM, (Declining) initially moderate EDM-based adherence followed by steep declines, (Good) initially high EDM-based adherence with modest declines, and (Best) consistently high EDM-based adherence. Being in the SOC arm, not being in school, higher evasiveness and panic decision-making scores, and lower adherence motivation were associated with higher odds of being in a worse trajectory group ( P < 0.05). A general decline in dosing was observed in the 12 weeks postintervention, when all participants were managed using SOC. CONCLUSIONS: Use of group-based trajectory models allowed a more nuanced understanding of EDM-based adherence over time compared with collapsed summary measures. In addition to the study intervention, other factors influencing EDM-based adherence included being in school, decision-making styles, and adherence-related motivation. This information can be used to design better intervention services for youth living with HIV.

Missed Opportunities When We Focus only on Risk: Using the Concerns Based Conversation Starter to Identify Potential PrEP Candidates.

Collection and use of self-reported HIV sexual risk-behaviors to identify pre-exposure prophylaxis (PrEP) candidates is common practice in PrEP providing and referral services. Critiques of this strategy highlight overreliance on self-report and contribution to ongoing PrEP stigma. As an alternative (or complimentary) approach, we evaluated a 5-item Concerns Based Conversation Starter (CBCS) that could be used to identify individuals who could benefit from PrEP. The CBCS was included in the 2019 cycle of the American Men's Internet Survey. Item responses were characterized overall and in relation to CDC risk-based PrEP indication and reported willingness to use PrEP. In total, 1606 HIV-negative men who have sex with men not on PrEP were evaluated. Of these, 50% were below the age of 25, 11% Black, 16% Latino, and 64% White. Across the sample, 61% (986) met risk-based criteria for PrEP indication, 80% (1278) were identified by the CBCS, and 52% (835) were flagged by both. The CBCS uniquely identified 28% (443) for follow-up PrEP discussions that would have been missed by a risk-based only approach. Only 9% (151) of the sample had risk-based indication but did not report concerns. Over half of those flagged by the CBCS expressed willingness to use PrEP. The CBCS identified more people than a risk-based indication approach, with most also reporting an interest in using PrEP. A small percentage of risk-indicated participants were 'missed' by the CBCS. As PrEP options and access points expand, implementation tools like the CBCS can facilitate more wide-scale, values-focused PrEP implementation.

Challenges with PrEP Uptake and Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kisumu, Kenya.

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.

RESUMEN: La evidencia respecto a desafíos existentes con aceptación y adherencia de la profilaxis previa a la exposición (PrEP) de VIH, entre los hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres (GBMSM) en Kenia es limitada. Condujimos un estudio de métodos mixtos y diseño explicativo secuencial. En la fase cuantitativa seguimos a 157 GBMSM VIH-negativos en riesgo que aceptaron PrEP y se inscribieron en una cohorte con un seguimiento de 12 meses. Analizamos, por lotes y al final del estudio, gotas de sangre seca recolectada a dos intervalos de tiempo y previamente almacenada, para determinar las concentraciones de difosfato de tenofovir (TFV-DP). A pesar de la alta adherencia autoinformada, solo el 14,6% de las personas tenían niveles protectores de TFV-DP en alguna visita. Los niveles protectores de TFV-DP se asociaron positivamente con el uso de drogas inyectables y un riesgo moderado autoevaluado de contraer el VIH, y negativamente con el tiempo transcurrido desde la inscripción. En la fase cualitativa posterior, conversamos con GBMSM de la comunidad para identificar las barreras y los facilitadores para la concientización, aceptación, adherencia y retención a PrEP. Estos datos revelaron numerosos desafíos con los programas tradicionales de PrEP que deben abordarse mediante colaboraciones comunitarias.

Impact of Motivational Enhanced Adherence Counseling and Point-of-Care Viral Load Monitoring on Viral Load Outcome in Women on Life-Long ART: A Randomized Pilot Study.

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 <200 copies/ml at 6 and 12 months between the arms through Fisher's exact test and sought associated factors by logistic regression with a 95% confidence interval (CI). Between December 2018 and July 2019, 50 women were enrolled (25 intervention and 25 controls) and followed until November 2020. At entry, 60% of the women were virally suppressed, 52% intervention vs. 68% control arm. Viral suppression was balanced between the two arms (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.

Impact of community health worker intervention on PrEP knowledge and use in Rakai, Uganda: A mixed methods, implementation science evaluation.

BACKGROUND: Effective models of support for HIV pre-exposure prophylaxis (PrEP) are needed for populations at elevated risk. In a hyperendemic Ugandan fishing community, PrEP counseling was provided through a situated Information, Motivation, and Behavioral Skills (sIMB)-based community health worker (CHW) intervention. We evaluated the intervention using a mixed-methods, implementation science design. METHODS: We surveyed all community members aged 15-49 through the Rakai Community Cohort Study. We used multivariable logistic regressions with generalized estimating equations to estimate the intervention's effect on PrEP knowledge and utilization. To understand intervention experiences and mechanisms, we conducted 74 qualitative interviews with 5 informant types (clients, CHWs, program staff, community leaders, health clinic staff) and analyzed data using an iterative, deductive approach. A mobile phone application provided intervention process implementation data. RESULTS: Individuals self-reporting receipt of the CHW intervention showed significantly higher PrEP knowledge (N = 1848, PRR: 1.10, 95% CI: 1.06-1.14, p = <.0001), PrEP ever use (N = 1176, PRR: 1.77, 95% CI: 1.33-2.36, p = <.0001), and PrEP current use (N = 1176, PRR: 1.86, 95% CI: 1.22-2.82, p = 0.0039) compared to those who did not. Qualitative findings attributed positive PrEP outcomes to CHW counseling and effective use of motivational interviewing skills by CHWs. Salient themes across the RE-AIM framework included support for the CHW intervention and PrEP across clients, community, and implementers. Mobile application data demonstrated consistent delivery of the PrEP module throughout implementation. CONCLUSIONS: CHWs improved PrEP knowledge and use among clients in an HIV hyperendemic fishing community. Mixed-methods, implementation science evaluations can inform adaptation of similar PrEP implementation strategies.

Randomized Controlled Trial of a Remote Coaching mHealth Adherence Intervention in Youth Living with HIV.

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.

Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305).

HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ2 = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ2 = 9.36, p = 0.009 and χ2 = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.