Monica Gandhi

Background: People with HIV (PWH) experience excess cardiovascular disease risk with persistent inflammation considered a key driver, despite antiretroviral therapy. Low-level viremia (LLV) may contribute to inflammation and vascular injury, but data in sub-Saharan Africa are limited. We assessed correlates of endothelial function among Black African PWH with a history of viremia despite antiretroviral therapy use. Methods: We conducted a cross-sectional substudy within the South African UTRA trial (NCT05333679). Endothelial function was measured with EndoPAT using the natural log-transformed Reactive Hyperemia Index (LnRHI); endothelial dysfunction was defined as LnRHI ≤ 0.51. The primary exposure was 12-month cumulative HIV viral load (VL) area under the curve. Body mass index, waist-to-hip ratio, and Body Roundness Index were modeled using adjusted natural cubic splines with robust standard errors. We evaluated associations of various covariates, including these body composition metrics, with LnRHI via multivariable regression. Results: Of 120 participants (median age 46 years, 69% women), 26% met criteria for endothelial dysfunction despite low 10-year cardiovascular disease risk. Median LnRHI was 0.69 (interquartile range 0.50–0.94). Mean cumulative VL area under the curve was 1.55 log ₁₀ copy-yr/mL (interquartile range 1.30–2.20), consistent with LLV. Cumulative VL was not associated with endothelial function after adjustment. By contrast, LnRHI varied significantly and nonlinearly across body mass index, waist-to-hip ratio, and Body Roundness Index, with an overall downward trend with increasing adiposity. Conclusions: In this cross-sectional analysis of Black African PWH with LLV, no association between cumulative VL and endothelial dysfunction was observed. However, higher adiposity was consistently associated with declining endothelial function. Our data add to the growing evidence on the importance of addressing body composition as a multifactorial risk determinant and important correlate of early vascular risk in PWH.

Among South African women using oral HIV preexposure prophylaxis, we compared a urine tenofovir point-of-care test with dried blood spot tenofovir diphosphate concentrations for recent vs longer-term adherence and assessed acceptability. The test demonstrated 76% accuracy, 100% sensitivity, and 69% specificity for high adherence (tenofovir diphosphate ≥700 fmol/punch) and was highly acceptable. Clinical Trials Registration: NCT04038060.

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.

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.

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.

Long-acting cabotegravir/rilpivirine supports virologic suppression among people with HIV (PWH) facing adherence challenges. In two large U.S. cohorts(n=1,070), 96% of viremic PWH achieved virologic suppression at a 4-week median. However, blips/failure were more frequent among PWH initiating with viremia, underscoring the need for careful monitoring and optimization of long-acting treatment.

Background: The United States faces an unprecedented surge in methamphetamine (MA) use, with severe implications for people living with HIV (PWH) or at risk of HIV acquisition. Current detection methods, including self-report and urine testing, have significant limitations. Hair testing represents a promising alternative for quantifying longer-term substance exposure but requires validation in clinical research settings. Setting: U.S. based cohort of men with and at-risk of HIV in Los Angeles (mSTUDY) Methods: We conducted a cross-sectional validation study using data from mSTUDY. We analyzed hair samples from two groups with negative urine MA tests: individuals reporting daily/weekly MA use (n=22) and controls reporting no MA use (n=22). Hair was analyzed using liquid chromatography-tandem mass spectrometry, with MA positivity defined as concentrations >200 picograms/mg per Society of Hair Testing guidelines. Results: Hair analysis detected MA use in 17/22 (77%) participants reporting regular use despite negative urine tests. Among controls reporting no MA use, 3 of 22 (14%) had positive hair samples. The positive likelihood ratio for detecting MA use not identified by urine testing was 6.0 (95% CI: 2.1-17.3), with sensitivity of 77.3% (95% CI: 56.6-89.9%) and specificity of 86.4% (95% CI: 66.7-95.3%). Among PWH, those reporting MA use had lower rates of virologic suppression compared to those without reported use (45% vs 82%, p=0.05). Conclusions: Hair testing successfully identified past-month MA use not detected by urine testing, with strong diagnostic performance. This validated biomarker provides objective measurement of longer-term MA use patterns, offering an important complement to current detection methods in substance use and HIV research.

Background: Human immunodeficiency virus (HIV) viral suppression remains suboptimal among people with HIV (PWH) facing barriers such as homelessness, substance use, and mental health disorders. In 2019, Ward 86 launched the POP-UP program, a low-barrier HIV care model serving PWH with unstable housing and difficulty engaging in care. In 2021, we introduced long-acting antiretroviral therapy (LA-ART), including for PWH unable to attain viral suppression on oral antiretroviral therapy. This study evaluates temporal trends in viral suppression and mortality rates within the POP-UP program. Methods: We conducted a retrospective cohort study of PWH enrolled in the POP-UP program between August 2019 and December 2024. Eligibility included viremia (HIV viral load ≥200 copies/mL) or being off antiretroviral therapy, homelessness/unstable housing, and difficulty engaging in care. Criteria later expanded to include PWH with severe mental health or substance use disorders. The primary outcomes were viral suppression (<200 copies/mL) and death. Results: Among 241 PWH ever enrolled in POP-UP, 86% attained viral suppression at least once during follow-up. Cross-sectional viral suppression was 47% in August 2019 (8 months after program inception) and increased to 64% in December 2024. By December 2024, 46% of suppressed patients were on LA-ART. The mortality rate declined from 8.8/100 person-years in 2020 to 2.6/100 person-years in 2024, with reductions in both AIDS-related and overdose deaths. Conclusions: The POP-UP program improved viral suppression and may have reduced the mortality rate among PWH with substantial barriers to care. Improvements were likely driven by integration of LA-ART and continued quality improvement. Persistent viremia within the program highlights the need for additional strategies to address structural and psychosocial barriers.

Background: Objective measures of antiretroviral therapy (ART) adherence, such as tenofovir (TFV) concentrations, may allow for targeted interventions to prevent future HIV viraemia. We evaluated three TFV adherence measures and their association with current and 24-week viral load (VL) outcomes. Methods: In a South Africa-based trial, we measured urine TFV using a point-of-care (POC) antibody-based assay and two metrics assessed via liquid-chromatography-mass-spectrometry: quantitative urine TFV and TFV-diphosphate (TFV-DP) concentrations in dried blood spots (DBS). Logistic regression assessed the association between current and subsequent 24-week VL outcomes and these three measures. We also compared the baseline characteristics of individuals with detectable vs. undetectable POC urine TFV results at enrolment. Results: Of 124 participants, 54.8% female, median age 39 years, 100 (81.5%) had detectable POC urine TFV and 23 (18.5%) did not. Higher TFV-DP concentrations in DBS were negatively associated with viraemia at 24-weeks (OR 0.83, 95% CI 0.725-0.928, p=0.003), whilst a detectable POC urine TFV (OR 0.62, 95% CI 0.22-1.82, p=0.380) and quantitative urine TFV (OR 0.98, 95% CI 0.95-1.00, p=0.153) showed no significant association. Compared to those with detectable POC urine TFV, those with undetectable POC urine TFV were more likely to be viraemic at enrolment (78.3% vs 25.7%, p<0.001) and have a CD4 count <200 cells/uL (34.8% vs 12.9%, p=0.001). Conclusion: DBS TFV-DP was associated with viraemia at 24-weeks and could help predict future viraemia. Undetectable POC urine TFV was associated with recent ART initiation, current viraemia, and lower CD4 count.

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.