Use of HIV Case Surveillance System to Design and Evaluate Site-Randomized Interventions in an HIV Prevention Study: HPTN 065

Introduction: Modeling studies suggest intensified HIV testing, linkage-to-care and antiretroviral treatment to achieve viral suppression may reduce HIV transmission and lead to control of the epidemic. To study implementation of strategy, population-level data are needed to monitor outcomes of these interventions. US HIV surveillance systems are a potential source of these data. Methods: HPTN065 (TLC-Plus) Study is evaluating the feasibility of a test, linkage-to-care, and treat strategy for HIV prevention in two intervention communities - the Bronx, NY, and Washington, DC. Routinely collected laboratory data on diagnosed HIV cases in the national HIV surveillance system were used to select and randomize sites, and will be used to assess trial outcomes. Results: To inform study randomization, baseline data on site-aggregated study outcomes was provided from HIV surveillance data by New York City and Washington D.C. Departments of Health. The median site rate of linkage-to-care for newly diagnosed cases was 69% (IQR 50%-86%) in the Bronx and 54% (IQR 33%-71%) in Washington, D.C. In participating HIV care sites, the median site percent of patients with viral suppression (<400 copies/mL) was 57% (IQR 53%-61%) in the Bronx and 64% (IQR 55%-72%) in Washington, D.C. Conclusions: In a novel use of site-aggregated surveillance data, baseline data was used to design and evaluate site randomized studies for both HIV test and HIV care sites. Surveillance data have the potential to inform and monitor sitelevel health outcomes in HIV-infected patients

Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073

ABSTRACT Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection

Pre-exposure prophylaxis initiation and adherence among Black men who have sex with men (MSM) in three US cities: results from the HPTN 073 study

Abstract : Introduction: Randomized clinical trials have demonstrated the efficacy of antiretroviral pre-exposure prophylaxis (PrEP) in preventing HIV acquisition among men who have sex with men (MSM). However, limited research has examined initiation and adherence to PrEP among Black MSM (BMSM) in the United States (US) who are disproportionately represented among newly HIV infected and late to care individuals. This research reports on the HIV Prevention Trials Network 073 (HPTN 073) study aimed to examine PrEP initiation, utilization and adherence among Black MSM utilizing the theoretically principled, cul- turally informed and client-centered care coordination (C4) model. Methods: The HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles, CA; Washington DC; and Chapel Hill, NC) from February 2013 through September 2015. Study participants were offered once daily oral emtricitabine/tenofovir (FTC/TDF) PrEP combined with C4 and followed up for 52 weeks. Participants received HIV testing, risk reduction education and clinical monitoring. Results: Of the 226 men enrolled, 178 participants initiated PrEP (79%), and of these 64% demonstrated PrEP utilization at week 26 (mid-point of the study) based on pharmacokinetic testing. Condomless anal sex with an HIV-infected or unknown status casual male partner was statistically significantly associated with a greater likelihood of PrEP initiation (adjusted odds ratio (OR) 4.4, 95% confidence interval (CI) 1.7, 11.7). Greater age (≥25 vs. <25, OR 2.95, 95% CI 1.37 –6.37), perception of having enough money (OR 3.6, 95% CI 1.7 to 7.7) and knowledge of male partner taking PrEP before sex (OR 2.22, 95% CI 1.03 to 4.79) were statistically significantly associated with increased likelihood of PrEP adherence at week 26. Annualized HIV incidence was 2.9 (95% CI 1.2 to 7.9) among those who initiated PrEP, compared to 7.7 (95% CI 2.5 to 24.1) among those who did not initiate PrEP (p = 0.18). Conclusions: Results suggest a high level of PrEP initiation among at-risk Black MSM, a group historically characterized as hard to reach. The data support the importance of addressing contextual factors that affect PrEP initiation and adherence, and of additional research on the ultimate benefit of PrEP in HIV prevention among Black MSM

Understanding the influence of Socio-ecological Factors on Preexposure Prophylaxis (PrEP) use in Adolescent Girls and Young Women in Africa

Thesis (Ph.D.)--University of Washington, 2022University of Washington Abstract Understanding the influence of Socio-ecological Factors on Preexposure Prophylaxis (PrEP) use in Adolescent Girls and Young Women in Africa Geetha Beauchamp Co-Chairs of Supervisory Committee:Kwun Chan, and Deborah Donnell Department of Health Systems and Population Health African adolescent girls and young women (AGYW) have one of the highest global HIV incidence rates despite increased access to highly effective oral preexposure prophylaxis (PrEP) for prevention, HIV testing, and linkage-to-care/viral suppression among men. Inconsistent PrEP adherence undermines PrEP benefits for AGYW. Qualitative research suggests that barriers to PrEP adherence include fear of disclosure of PrEP use, stigma, provider distrust, and poor social support. A reliable tool for predicting AGYW’s “PrEP readiness” would help identify who could benefit from greater PrEP adherence support. An improved understanding of the pathways affecting AGYW’s adherence is crucial to advancing adherence strategies. This research used data from the open-label HPTN 082 study conducted among AGYW (ages16-25 years) in South Africa and Zimbabwe. The HIV Prevention Readiness Measure (HPRM) questionnaire was adapted from the validated HIV Treatment Readiness Measure, which predicted viral suppression in HIV-positive youth in the U.S. The HPRM was administered to HPTN 082 participants at enrollment and again three months later. The aims of this research were to 1) evaluate the psychometric properties and the utility of the HPRM to predict PrEP adherence; 2) investigate the association between PrEP disclosure and adherence and whether it was moderated by social support and mediated through PrEP support; and 3) assess whether mistrust in the study team was associated with discordance between patient-reported PrEP adherence and an objective biomarker of PrEP adherence, intracellular tenofovir-diphosphate drug concentrations. The findings were: 1) overall HPRM score and the three subscales (self-efficacy, disclosure of PrEP use, and social support) are reliable and predicted increased PrEP adherence; and disclosure of PrEP use increased the odds of persistent adherence; 2) AGYW with supportive adults in their life and disclosed PrEP use to their parents had higher adherence; and 3) AGYW who expressed high trust in their providers had higher odds of both high self-reported and drug level measures of PrEP adherence. The research makes three significant contributions to improving PrEP delivery: 1) HPRM as a tool to assess PrEP readiness and focus adherence support on AGYW who have low self-efficacy, low social support, and no plans for disclosing PrEP use; 2) supporting AGYW to consider disclosing their PrEP use to the supportive adults in their lives; and 3) in provider PrEP training, discuss the importance of AGYW’s trust in their provider as essential to improving AGYW reporting actual PrEP use

Predictors of HIV Transmission Risk Behavior and Seroconversion Among Latino Men Who have Sex with Men in Project EXPLORE

In the US, Latino MSM are disproportionately affected by HIV, yet there is a paucity of data for this risk group. To this end, we examined data on Latino and non-Latino white MSM who participated across six cities in a 2-year randomized behavioral intervention study—Project EXPLORE. At baseline, Latinos reported significantly more serodiscordant unprotected anal intercourse (SDUA) than non-Latinos. Longitudinal predictors of SDUA included marijuana, poppers, amphetamines and heavy drinking, as well as lower self-efficacy, poorer communication skills, weaker safe-sex norms and more enjoyment of risky sex. For HIV infection, Latinos had significantly higher seroconversion rate over follow-up than non-Latinos. Longitudinal predictors of seroconversion among Latinos included poppers and SDUA. Intervention effects did not significantly differ between Latino and non-Latinos. Findings support HIV intervention work with Latino MSM that includes skills training/counseling to address attitudes about safe sex and impact of substance use on HIV-risk behavior and acquisition.En los Estados Unidos, el VIH afecta de una manera desproporcionada a los hombres de origen latino que tienen relaciones sexuales con otros hombres. Pero aún hay poca información o datos disponibles que enfocan en este grupo de alto riesgo. A este fin, examinamos los datos de hombres que tienen relaciones sexuales con otros hombres (HSH) quienes participaron en un estudio aleatorizado de dos años de una intervención conductual que se llevó a cabo en seis ciudades – Project EXPLORE. Sólo examinamos los datos de participantes de origen latino y de blancos no de origen latino. En la visita inicial, comparado a los blancos, los hombres de origen latino indicaron significativamente más altos niveles de sexo anal serodiscordante sin protección (SDUA). Al transcurso del estudio, predictores longitudinales de SDUA incluyeron los siguientes: uso de marijuana, poppers (nitritos), anfetaminas, y un nivel alto de consumir el alcohol, y también un nivel bajo de auto-eficacia, pobres destrezas de communicación, bajas normas sobre el sexo seguro, y más disfrutamiento del sexo de alto riesgo. Con respecto a la infección por VIH, los latinos experimentaron significativamente más altos niveles de sero-infección sobre el transcurso del estudio en comparación a los hombres blancos. Los predictores longitudinales de sero-infección para los latinos incluyeron el uso de poppers (nitritos) y SDUA. El efecto de la intervención no fue diferente cuando comparamos a los latinos y los blancos. Los resultados sugieren que, para prevenir el comportamiento de alto riesgo y el sero-infección dentro los latinos HSH, las intervenciones para la prevención del VIH deben de incluir consejería y entrenamiento en destrezas para mejorar las actitudes sobre el sexo seguro y el impacto del uso de drogas callejeras

Sexual Risk Profiles Among Black Sexual Minority Men: Implications for Targeted PrEP Messaging.

Black gay, bisexual, and other Black sexual minority men (BSMM) continue to experience some of the largest sexual health disparities in the U.S. Engaging BSMM in PrEP is crucial to improving sexual health outcomes and reducing disparities. However, knowledge of the profiles of sexual risk and PrEP initiation among this group is limited. This study used latent class analysis (LCA) to identify HIV risk and PrEP initiation patterns among BSMM in the HPTN 073 study (n=226). Guided by current CDC screening guidelines, latent class indicators included relationship status, condom use, number of sexual partners, substance use, sexually transmitted infection (STI) history, and partner HIV status. Age and PrEP initiation were used in a multinomial regression to identify correlates of class membership. Three latent classes were identified: Single with Condomless Partners, Single with Multiple Partners, and Serodiscordant Partners. Single with Multiple Partners had the highest conditional probabilities of having greater than three male partners, substance use before sex, and receiving an STI diagnosis. Serodiscordant Partners had a 100% conditional probability of condomless sex and having a male partner living with HIV. BSMM who initiated PrEP were less likely to be classified as Single with Condomless Partners than Serodiscordant Partners (AOR=0.07, 95% CI=0.02, 0.66). Findings support the need for culturally relevant tailored and targeted messaging for BSMM with multiple sexual risk indicators

Brief Report: Associations Between Self-Reported Substance Use Behaviors and PrEP Acceptance and Adherence Among Black MSM in the HPTN 073 Study.

BACKGROUND: Preexposure prophylaxis (PrEP) is efficacious for HIV prevention. Black Men who have Sex with Men (MSM) accounted for the largest proportion of new HIV diagnoses in the U.S relative to other racial/ethnic groups. Black MSM who use substances are at an increased risk for HIV infection and are ideal candidates for PrEP, but barriers to maintaining PrEP adherence remain a concern. We assessed whether substance use behaviors are associated with initiation and adherence to PrEP among a sample of Black MSM in the U.S. METHODS: Data for this analysis comes from the HIV Prevention Trails Network Study 073 (HPTN 073). Substance use behaviors – including alcohol, marijuana, poppers (i.e. alkyl nitrites) and stimulants (i.e. methamphetamine/cocaine use) including use of these substances before/during condomless anal intercourse (CAI) – were assessed longitudinally via self-report. PrEP adherence was assessed by pharmacological testing in blood. Generalized estimating equations were used to evaluate association between substance use behaviors and PrEP initiation and adherence. RESULTS: Among 226 HIV-negative Black MSM, the majority (60%) were 25+ years of age. Most of the substance use behaviors, were not significantly associated with PrEP initiation or adherence. However, stimulant use before/during CAI was significantly associated with lower odds of PrEP adherence (Adjusted odds ratio=0.21, 95% confidence interval=0.07, 0.61; p=<0.01). CONCLUSIONS: These findings suggest that PrEP adherence is feasible among Black MSM who use substances. However, Black MSM who engage in stimulant use before/during CAI may present a unique group for additional study and support with enhanced behavioral health and support services

Trust in the provider and accurate self-reported PrEP adherence among adolescent girls and young women in South Africa and Zimbabwe: HPTN 082 study

Abstract Background Trust is an important cornerstone of patient-provider communication. Accurate reporting of pre-exposure prophylaxis (PrEP) adherence is vital for providers to determine who needs adherence support, especially adolescent girls and young women (AGYW) disproportionately affected by newly diagnosed HIV. Methods This is a secondary analysis of the HPTN 082 open-label PrEP demonstration trial. From 2016–2018, 451 AGYW aged 16–25 years were enrolled in South Africa (Cape Town and Johannesburg) and Zimbabwe (Harare). PrEP was initiated by 427, and 354 (83%) had month three patient-reported adherence responses and intracellular tenofovir diphosphate (TFV-DP) measurements. The patient-reported adherence response to ‘In the past month, how often did you take the tablet?’ was dichotomized as ‘high’ if the response was every day or most days, and ‘low’ if some days or not many days or never. The biomarker marker evidence of adherence in dried blood spots was defined as ‘high’ if TFV-DP ≥ 700, and ‘low’ if < 350 fmol/punch. We used multinomial logistic regression to examine if trust in the PrEP provider was associated with concordance between patient-reported adherence and intracellular tenofovir-diphosphate (TFV-DP). Results AGYW who reported trust in their providers were almost four-fold (aOR 3.72, 95% CI 1.20–11.51) more likely to have concordant adherence (high self-reported adherence and high TFV-DP concentrations) compared to discordant non-adherence (high self-reported adherence and low TFV-DP concentrations). Conclusion Education and training of providers to build trusting relationships with AGYW may lead to more accurate reporting of PrEP adherence. With accurate reporting, adequate support can be provided to bolster adherence. Trial registration ClinicalTrials.gov Identifier: NCT02732730

Brief Report: Associations Between Self-Reported Substance Use Behaviors and PrEP Acceptance and Adherence Among Black MSM in the HPTN 073 Study.

BackgroundPre-exposure prophylaxis (PrEP) is efficacious for HIV prevention. Black men who have sex with men (MSM) accounted for the largest proportion of new HIV diagnoses in the United States relative to other racial/ethnic groups. Black MSM who use substances are at an increased risk for HIV infection and are ideal candidates for PrEP, but barriers to maintaining PrEP adherence remain a concern. We assessed whether substance use behaviors are associated with initiation and adherence to PrEP among a sample of black MSM in the United States.MethodsData for this analysis come from the HIV Prevention Trails Network Study 073 (HPTN 073). Substance use behaviors-including alcohol, marijuana, poppers (ie, alkyl nitrites), and stimulants (ie, methamphetamine/cocaine use) including use of these substances before/during condomless anal intercourse (CAI)-were assessed longitudinally through self-report. PrEP adherence was assessed by pharmacological testing in blood. Generalized estimating equations were used to evaluate association between substance use behaviors and PrEP initiation and adherence.ResultsAmong 226 HIV-negative black MSM, the majority (60%) were 25+ years of age. Most of the substance use behaviors were not significantly associated with PrEP initiation or adherence. However, stimulant use before/during CAI was significantly associated with lower odds of PrEP adherence (adjusted odds ratio = 0.21, 95% confidence interval = 0.07 to 0.61; P = &lt;0.01).ConclusionsThese findings suggest that PrEP adherence is feasible among black MSM who use substances. However, black MSM who engage in stimulant use before/during CAI may present a unique group for additional study and support with enhanced behavioral health and support services