Preferential Initiation of Long-Acting Injectable Versus Oral HIV Pre-Exposure Prophylaxis Among Women Who Inject Drugs.

Fifty-five of 62 women who inject drugs (WWID) selected long-acting cabotegravir (CAB-LA) over oral PrEP, and 51/55 received a first injection. More recent injection drug use and number of sexual partners were associated with selecting CAB-LA (P < .05). Findings provide preliminary evidence of a strong preference for longer-acting products among WWID.

Syndemic Psychosocial Conditions among Youth Living with HIV: a Latent Class Analysis.

Drug use, mental distress, and other psychosocial factors threaten HIV care for youth living with HIV (YLWH). We aimed to identify syndemic psychosocial patterns among YLWH and examine how such patterns shape HIV outcomes. Using baseline data from 208 YLWH enrolled in an HIV treatment adherence intervention, we performed latent class analysis on dichotomized responses to 9 psychosocial indicators (enacted HIV stigma; clinical depression and anxiety; alcohol, marijuana, and illicit drug misuse; food and housing insecurity; legal history). We used multinomial logistic regression to assess latent class-demographic associations and the automatic Bolck-Croon-Hagenaars method to assess HIV outcomes by class. Mean age of participants was 21 years; two thirds identified as cis male, 60% were non-Hispanic Black, and half identified as gay. Three classes emerged: "Polydrug-Socioeconomic Syndemic" (n = 29; 13.9%), "Distress-Socioeconomic Syndemic" (n = 35, 17.1%), and "Syndemic-free" (n = 142, 69.0%). Older, unemployed non-students were overrepresented in the "Polydrug-Socioeconomic Syndemic" class. Missed/no HIV care appointments was significantly higher in the "Polydrug-Socioeconomic Syndemic" class (81.4%) relative to the "Syndemic-free" (32.8%) and "Distress-Socioeconomic Syndemic" (31.0%) classes. HIV treatment nonadherence was significantly higher in the "Polydrug-Socioeconomic Syndemic" class (88.5%) relative to the "Syndemic-free" class (59.4%) but not the "Distress-Socioeconomic Syndemic" class (70.8%). Lack of HIV viral load suppression was non-significantly higher in the "Polydrug-Socioeconomic Syndemic" class (29.7%) relative to the "Syndemic-free" (16.2%) and "Distress-Socioeconomic Syndemic" (15.4%) classes. Polydrug-using, socioeconomically vulnerable YLWH are at risk for adverse HIV outcomes, warranting tailored programming integrated into extant systems of HIV care.

Pharmacologic Drug Detection and Self-Reported Adherence in the HPTN069/ACTG5305 Phase II PrEP Trial.

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48. Descriptive statistics and a generalized linear model were used to assess the association between selected demographic factors, self-report of daily medication adherence and plasma drug concentrations consistent with daily adherence. Among 718 paired observations from 370 participants, 43% (306/718) reported daily adherence by CASI, 65% (467/718) had drug concentrations consistent with daily adherence and 11% (81/718) had CASI responses that reported daily adherence despite having drug concentrations consistent with less-than-daily adherence. In adjusted analyses, participants who were assigned male at birth (aOR 1.42 [95% CI 1.02, 1.97]), older (5-year increments aOR 1.10 [95% CI 1.09, 1.11]), White (aOR 2.2 [95% CI 1.88, 2.56]), had advanced education (aOR 3.89 [95% CI 2.97, 5.09]), were employed (aOR 1.89 [95% CI 1.50, 2.40]), or partnered/married (aOR 2 [95% CI 1.72, 2.32]) were more likely to have drug concentrations consistent with daily adherence. Participants who were not employed (aOR 2.7 [95% CI 1.31, 5.55]) or who were single/not partnered (aOR 2.33 [CI 95% 1.25, 4.34]) were more likely to have drug concentrations that did not reflect daily adherence despite self-reported PrEP adherence. These findings support the need for ongoing adherence counseling in clinical trials of new PrEP regimens.

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.

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV.

BACKGROUND: Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence. METHODS: Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations. RESULTS: Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable. CONCLUSION: IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence. CLINICAL TRIALS REGISTRATION: NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

A Web-Based Antiretroviral Therapy Adherence Intervention (Thrive With Me) in a Community-Recruited Sample of Sexual Minority Men Living With HIV: Results of a Randomized Controlled Study.

BACKGROUND: Most new HIV infections are attributed to male-to-male sexual contact in the United States. However, only two-thirds of sexual minority men living with HIV achieve an undetectable viral load (UVL). We tested a web-based antiretroviral therapy adherence intervention called Thrive with Me (TWM) with core features that included medication self-monitoring and feedback, HIV and antiretroviral therapy information, and a peer-to-peer exchange. OBJECTIVE: We assessed the efficacy of TWM on HIV UVL among adult (aged ≥18 years) sexual minority men. Moreover, we assessed the impact of overall engagement and engagement with specific intervention features on HIV UVL. METHODS: In total, 401 sexual minority men (mean age 39.1, SD 10.8 y; 230/384, 59.9% African American) in New York City were recruited between October 2016 and December 2019 and randomized to receive TWM (intervention) or a weekly email newsletter (control) for 5 months. Computerized assessments occurred at baseline and months 5, 11, and 17. The primary outcome was a dichotomous measure of HIV UVL (≤20 copies/µL). Generalized estimating equations with robust SEs were used to assess the effect of the TWM intervention on HIV UVL over the follow-up period in an unadjusted model and a model adjusted for baseline differences and then stratified by baseline recent drug use urinalysis. In secondary analyses, generalized linear models were used to estimate risk differences in the association of overall engagement with TWM (the sum of the number of days participants accessed ≥1 screen of the TWM intervention out of a possible 150 days) and engagement with specific TWM components on HIV UVL throughout the 17-month intervention period. RESULTS: Participant retention was 88.5% (355/401; month 5), 81.8% (328/401; month 11), and 80.3% (322/401; month 17). No consistent differences in HIV UVL were found between those randomized to receive TWM or the control at the 5- (difference-in-differences [DD]=-7.8, 95% CI -21.1 to 5.5), 11- (DD=-13.9, 95% CI -27.7 to 0.04), or 17-month (DD=-8.2, 95% CI -22.0 to 5.7) time points, or when stratified by baseline recent drug use. However, those TWM-assigned participants with high overall levels of engagement (in the upper 25th percentile) were more likely to have an HIV UVL at the end of the 5-month active intervention period compared to those with low engagement (below the 75th percentile; risk difference=17.8, 95% CI 2.5-33.0) or no engagement (risk difference=19.4, 95% CI 3.3-35.5) in the intervention. Moreover, high engagement with the peer-to-peer exchange was associated with HIV UVL over time in unadjusted models. CONCLUSIONS: TWM did not have overall impacts on HIV UVL; however, it may assist some sexual minority men who are highly engaged with this web-based intervention in achieving HIV viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT02704208; https://clinicaltrials.gov/study/NCT02704208.

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.

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.

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.

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.

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.

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Antiretroviral 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. METHODS: This 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. FINDINGS: Between 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 <200 copies per mL), and the median CD4 count was 466 cells per µL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050). INTERPRETATION: When started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths. 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.

Combining information to estimate adherence in studies of pre-exposure prophylaxis for HIV prevention: Application to HPTN 067.

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.

Stigmatizing Policies Interact with Mental Health and Sexual Behaviours to Structurally Induce HIV Diagnoses Among European Men Who Have Sex with Men.

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.

HIV Prevention and Treatment Behavior Change and the Situated Information Motivation Behavioral Skills (sIMB) Model: A Qualitative Evaluation of a Community Health Worker Intervention in Rakai, Uganda.

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.

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.

Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States.

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.

Electronic Dose Monitoring Identifies a High-Risk Subpopulation in the Treatment of Drug-resistant Tuberculosis and Human Immunodeficiency Virus.

BACKGROUND: In generalized drug-resistant tuberculosis (DR-TB) human immunodeficiency virus (HIV) epidemics, identifying subpopulations at high risk for treatment failure and loss to care is critically important to improve treatment outcomes and prevent amplification of drug resistance. We hypothesized that an electronic dose-monitoring (EDM) device could empirically identify adherence-challenged patients and that a mixed-methods approach would characterize treatment challenges. METHODS: A prospective study of patients with DR-TB HIV on antiretroviral therapy (ART) initiating bedaquiline-containing regimens in KwaZulu-Natal, South Africa. Separate EDM devices measured adherence for bedaquiline and ART. Patients with low adherence (<85%) to both bedaquiline and ART were identified as high risk for poor outcomes. Baseline survey, study visit notes, and focus group discussions characterized treatment challenges. RESULTS: From December 2016-February 2018, 32 of 198 (16%) enrolled patients with DR-TB HIV were identified as dual-adherence challenged. In a multivariate model including baseline characteristics, only receiving a disability grant was significantly associated with dual nonadherence at 6 months. Mixed-methods identified treatment barriers including alcohol abuse, family conflicts, and mental health issues. Compared with adherent patients, dual-adherence-challenged patients struggled to prioritize treatment and lacked support, and dual-adherence-challenged patients experienced higher rates of detectable HIV viral load and mortality than more adherent patients. CONCLUSIONS: EDM empirically identified a subpopulation of patients with DR-TB HIV with dual-adherence challenges early in treatment. Mixed-methods revealed intense psychosocial, behavioral, and structural barriers to care in this subpopulation. Our data support developing differential, patient-centered, adherence support interventions focused on psychosocial and structural challenges for subpopulations of at-risk DR-TB HIV patients.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa.

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.