Matthew A. Spinellii

Background: Young men who have sex with men (MSM) in the U.S. have suboptimal adherence to oral tenofovir-based pre-exposure prophylaxis (PrEP), undermining HIV prevention goals. Drug-level feedback using urine point-of-care tenofovir assays has improved adherence in Eastern and Southern African settings but has not been assessed among U.S. MSM. Setting: Community-based PrEP clinic in San Francisco and home-based remote counseling sessions among young MSM across the U.S. Methods: A two-phase study was conducted. Phase 1 involved qualitative interviews with 20 young MSM (mean age 25.7 years) from a San Francisco PrEP clinic, guided by the COM-B model and Behavior Change Wheel framework to identify barriers to adherence, informing the development of the PrEP2-BAY intervention. Phase 2 pilot-tested the PrEP2-BAY intervention remotely among 20 MSM (mean age 27.7 years), using at-home urine tenofovir tests and counselor-led feedback and action planning via Zoom. Acceptability was assessed qualitatively through the Theoretical Framework of Acceptability. Urine tenofovir levels were compared pre- and post-intervention. Results: Key barriers to PrEP adherence identified included mental health, substance use, relationship dynamics, and stigma. Participants preferred at-home testing with counselor guidance, leading to adaptation of PrEP2-BAY into an mHealth approach. In the pilot phase, participants reported high acceptability and perceived effectiveness. There was a trend toward improved urine tenofovir levels with all participants exhibiting positive urine test results post-intervention. Conclusions: PrEP2-BAY demonstrated high acceptability with a trend toward improved adherence among young MSM. Further evaluation through a randomized controlled trial is recommended to assess efficacy and support broader implementation.

Background: Scalable, low-cost strategies for monitoring antiretroviral therapy adherence are increasingly important, particularly in decentralized and telehealth-based care settings. This study assessed both the feasibility and performance of at-home, point-of-care (POC) urine tenofovir (TFV) testing for adherence monitoring, using tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) as a pharmacological standard of adherence. Setting: This study was conducted within the LetSync cohort of people with HIV in primary romantic relationships, primarily Black men who have sex with men, across the U.S. Methods: Participants self-collected POC urine TFV testing and DBS samples over five timepoints across eight months. Adequate adherence was defined as TFV-DP ≥4 doses/week in DBS. Generalized estimating equation models evaluated associations between urine TFV results and DBS-based adherence, as well as the probability of sample return over time. Results: Among 86 participants and 341 paired samples, detectable urine TFV was strongly associated with adequate adherence in DBS (aRR = 2.86; 95% CI: 1.37–5.99). The urine POC test demonstrated high sensitivity (97%) and positive predictive value (85%), with lower specificity (31%). Across timepoints, urine samples showed higher return rates compared to DBS (aRR = 1.04; 95% CI: 1.01–1.08). Participants with detectable viral load had lower return rates for DBS compared to urine. Conclusions: At-home POC urine TFV testing is a sensitive and feasible approach for monitoring adherence. Its simplicity and consistently high return rates support its potential as a practical adherence monitoring tool, particularly in settings where VL testing is infrequent or logistically limited.

Introduction: Daily oral pre‐exposure prophylaxis (PrEP) use remains low among adolescent girls and young women (AGYW). We evaluated whether a peer support intervention improved daily oral PrEP uptake and adherence among AGYW at high risk of HIV acquisition in Kampala, Uganda. Methods: We conducted an open‐label randomized controlled trial (January 2023−June 2024) among 14‐ to 24‐year‐olds engaged in sex work. Eligible participants were randomized 1:1 to receive either health worker counselling only (control) or supplemented with peer support (intervention). Peer leaders delivered co‐created peer education sessions starting 1 month after enrolment. Participants were followed for 12 months. Co‐primary outcomes were PrEP uptake (yes/no) and adherence, evaluated using two separate measures; optimal if: ≥85% pill‐counts (primary measure); positive point‐of‐care urine tenofovir test. Both arms received adherence counselling based on urine results. Secondary outcomes: PrEP persistence (time to discontinuation) and cost‐effectiveness (cost per disability adjusted life year/DALY averted). Analysis used logistic regression (uptake); generalized estimating equations (adherence), Cox regression (persistence) and incremental cost‐effectiveness ratio (ICER) below US$537 per DALY averted was considered cost‐effective. Results: We enrolled 394 participants (197 per arm) with a mean age of 19.4 (SD ±2.3) years. The intervention did not impact PrEP uptake (OR 1.15; 95% CI 0.77−1.71) but improved adherence, pill count (OR 2.20; 95% CI 1.23−3.95) and urine assay (OR 2.18; 95% CI 1.22−3.91). Optimal adherence was low but significantly higher in the intervention by both measures: pill count (intervention = 54.8%, control = 39.6%, p = 0.008), urine assay (intervention = 54.8%, control = 40.8%, p = 0.001). Median duration before PrEP discontinuation was 38 days (IQR 0–319 days); intervention (56 days), control (29 days). The intervention had no effect on persistence (HR 0.86; 95% CI 0.64−1.14). It was cost‐effective with the urine tenofovir assay (ICER = $459) but not with pill counts (ICER = $581). Conclusions: This peer‐led intervention improved PrEP adherence among AGYW in Kampala and is recommended in high‐incidence settings. Urine tenofovir testing can be used to assess adherence if affordable. Enhanced peer support strategies are needed until long‐acting PrEP becomes accessible and acceptable. Future research should optimize timing, intensity and delivery models of peer support interventions and integrate them with long‐acting PrEP to improve sustainability.

Objective: To evaluate the durability of SARS-CoV-2–specific humoral and cellular immune responses after booster vaccination in people living with HIV (PLWH) in a prospective longitudinal cohort study. Methods: We analyzed 46 PLWH with no prior history of SARS-CoV-2 infection who received a booster dose. Anti-receptor-binding domain (RBD) IgG concentrations, neutralization titers, and T cell responses were measured over time. The associations between CD4+ T cell count and CD4/CD8 ratio with antibody dynamics were assessed, adjusting for age, sex, and vaccine type. Results: Anti-RBD IgG and neutralization titers declined significantly over time. Participants with CD4+ T cell counts <500 cells/μL exhibited a 3-fold faster decline in anti-RBD IgG compared to those with ≥500 cells/μL. Neutralization capacity declined similarly across both groups, suggesting that CD4+ T cell count primarily influences antibody quantity rather than functional quality. A lower CD4/CD8 ratio was independently associated with reduced baseline IgG concentrations but did not influence the rate of antibody decay. In a subset of 30 participants, a lower CD4/CD8 ratio was also associated with altered follicular helper (Tfh) CD4+ T cell frequencies and faster decline of Spike-specific Tfh over time. Conclusions: CD4+ T cell count influences antibody persistence, while the CD4/CD8 ratio affects initial antibody magnitude and Tfh cell frequencies, highlighting complementary roles in shaping vaccine responses in PLWH.

Background: Biomarkers provide reliable information on oral PrEP pill-taking. It remains unclear whether self-reported PrEP adherence has value when used in combination with pharmacologic measures. We examined associations between self-reported and biomarker-based PrEP adherence metrics to improve identification of those with low adherence in resource-constrained settings. Methods: HIV-uninfected women using oral tenofovir (TFV)-based PrEP were enrolled (N=100) in the Point-of-Care Urine Monitoring for Adherence trial in Kenya from 2021–2022. Participants were randomized 1:1 to standard-of-care or urine-based-point-of-care assay-informed drug-level feedback. Adherence was measured at enrollment and quarterly through 12 months via urine, hair and self-report. A positive urine assay (TFV≥1500 ng/mL) indicated short-term adherence. TFV hair concentration≥0.023 ng/mg indicated long-term adherence (4-times-weekly dosing). Self-reported adherence was calculated as the mean score (range=0-100) on a 2-item scale. Generalized estimating equations estimated longitudinal associations between self-reported adherence and biomarkers. Receiver-operating-characteristic curves assessed self-report as a predictor of biomarker metrics. Results: At enrollment, 68.7% had a positive urine assay, 83.7% had detectable hair TFV, and median self-reported adherence was 100 (IQR=90-100). At Month 12, participants with higher adherence scores were more likely to have hair TFV concentrations≥0.023 ng/mg (aRR=1.44; 95% CI=1.20-1.72; p-value<0.001) and positive urine results (aRR=1.56; CI=1.43-1.69; p-value=<0.001). Areas-under-the-curve for self-report as a predictor of hair levels were 0.64 in a model with self-report and 0.74 in a model with both self-report and urine testing. Conclusions: Associations between self-reported and biomarker-verified PrEP adherence demonstrated accurate reporting. Incorporating biomarkers in studies may result in improved adherence and/or improved accuracy of self-report.

BACKGROUND Stimulant use among men who have sex with men (MSM) is on the rise, threatening progress towards the U.S. Ending the HIV Epidemic (EHE) goals. Antiretroviral (ART) nonadherence is a key contributor to poor HIV treatment outcomes. As one of the strongest determinants of ART nonadherence, hazardous stimulant use, alongside other multi-level factors, must be examined to determine the best approaches to ensure improved HIV treatment adherence. Current methods for measuring adherence are either inaccurate or unavailable at the point-of-care. Objective, point-of-care adherence monitoring may offer a new solution to rapidly measure ART nonadherence. OBJECTIVE This study used fully remote-contact methods to develop a U.S. national cohort to assess the impact of the stimulant epidemic on both ART adherence and viral suppression. The primary outcomes are viral suppression and the acceptability and feasibility of remote study procedures, with stimulant use examined as a key predictor of both. METHODS The American Remote Contact HIV Epidemiology Study (ARCHES) is a large, remote observational cohort of 1,000 MSM living with HIV who have suboptimal ART adherence. ARCHES examines multi-level factors that influence viral suppression, stimulant use, and ART adherence among MSM, while evaluating the acceptability and feasibility of remote study procedures. The study aimed to recruit over 40% Black MSM, with a high proportion (>70%) of the sample self-reporting stimulant use. Enrolled participants were living with HIV, ≥ 18 years old, with self-reported sub-optimal ART adherence within the last 12 months. Viral suppression was measured using viral loads from remote phlebotomy appointments, stimulant use via self-report and self-collected hair sample analysis, and ART adherence using a urine-based POC lateral flow assay. Acceptability and feasibility were evaluated through participant retention over four years and survey data. RESULTS Recruitment of the observational cohort began in October 2023 and concluded in September 2024. Recruitment goals were met, with 40.3% Black participants and 71.6% stimulant users enrolled. Data collection is underway, with anticipated completion in 2027. CONCLUSIONS Findings from this large-scale national, remote study will elucidate factors that influence ART adherence. Remote enrollment had the benefit of reaching a diverse sample of individuals less engaged in care, but it also required careful coordination of sample shipments and fraud detection. Furthermore, the geographical and sociodemographic diversity of this cohort will help identify geographic, structural, and social barriers to HIV care engagement and viral suppression. This cohort also oversampled for Black participants and participants who use stimulants, two groups commonly underrepresented in similar cohorts. Collectively, these findings will inform future adherence interventions and support efforts to end the U.S. HIV epidemic.

A remote, motivational interviewing–informed intervention using self-administered point-of-care urine tenofovir testing improved long-term pre-exposure prophylaxis (PrEP) adherence among young US men-who-have-sex-with-men in a pilot randomized trial. Participants increased hair tenofovir levels by 1–2 tablets weekly, with high feasibility and acceptability, supporting further implementation.

Introduction: Differentiated service delivery (DSD) models for HIV and tuberculosis (TB) care prioritize efficient resource allocation and targeted interventions, and benefit from accurate assessment of patients’ antiretroviral therapy (ART) pill‐taking status. Accurate ART use identification is essential for ensuring proper care transition services rather than unnecessary initiation. A point‐of‐care urine tenofovir (TFV) assay may identify undisclosed ART use in settings with high rates of TB and HIV coinfection.Methods: A cohort of people living with HIV (PWH) presenting for routine care, including newly diagnosed and those returning to care, and reporting no ART use within 90 days, was enrolled in a clinic‐based cross‐sectional study of TB prevalence which tested for TB using sputum and urine‐based TB tests in two clinics in KwaZulu‐Natal, South Africa. CD4 counts were determined at the time of ART initiation, per national guidelines. A novel urine‐based lateral flow assay (LFA) which detects TFV ingested within the past 4–7 days was used to assess ART use from thawed urine samples, which were collected concurrently with the self‐report assessment. Conditional logistic regression models assessed predictors of ART non‐disclosure.Results: Between 12/2021 and 5/2024, 404 PWH (40% male) reporting no recent ART use presented for ART initiation. TB testing identified 14 (3%) PWH with undiagnosed TB. Seventy‐nine (20%) had detectable TFV in urine indicating undisclosed ART use, with a median CD4 count of 466 cells/mm³ (IQR 277–625) compared to 322 cells/mm³ (IQR 175–490, p = 0.001) in those without undisclosed ART use. In a multivariable model, undisclosed ART use was associated with older age, rural clinic site, higher CD4 count and having active TB, but not with gender, education or employment.Conclusions: Among people presenting for HIV treatment initiation, 20% had evidence of ART use within 4–7 days by TFV urine LFA testing. Integration of point‐of‐care urine TFV assays into DSD models of HIV care may support providers to engage PWH about treatment challenges, address potential barriers to disclosure and facilitate seamless transfers between clinics. If successful, this strategy may reduce duplicative care entries and promote more efficient use of resources.