Substance use adversely affects engagement in HIV care, adherence to medication, and HIV viral suppression. This review assessed the scope of US interventions designed to promote positive outcomes along the HIV care continuum for people with HIV who have substance use disorder (SUD) or at-risk substance use. A literature search identified 27 interventions published in peer-reviewed articles found on PubMed and PsycINFO databases between January 1, 2019, and December 31, 2023. Common strategies to improve HIV care continuum outcomes included support for HIV medication adherence, motivational interviewing, medications to treat SUD, contingency management, cognitive-behavioral skills building, patient navigation, mindfulness practice, and low-barrier entry to care. Contingency management (offering financial or material incentives for attaining desired outcomes) alone or combined with other strategies was most consistently associated with positive HIV outcomes, but more research is needed to understand how these outcomes can be sustained. Few intervention studies addressed or measured linkage to care (12%) or retention in care (15%), despite a clear need to better engage this population. Further innovation is needed to improve HIV engagement and retention among people with SUD or at-risk substance use.

Transgender, nonbinary, and gender diverse (TGD) adults experience elevated suicide attempt (SA) risk relative to cisgender adults, yet modifiable vulnerabilities and resiliencies remain understudied. This cross-sectional study examined correlates of lifetime and past 6-month SA among TGD adults receiving primary care. Electronic surveys were completed by 2131 TGD patients at two urban health centers, assessing demographics, gendered contexts, social determinants, interpersonal violence, mental health, and protective factors. Bivariate and multivariable log-Poisson generalized estimating equation models estimated associations with lifetime and past 6-month SA risk. The median age was 28 years; 29.2% had a non-White racial identity and 30.8% were nonbinary. Overall, 30.8% reported a lifetime SA and 2.5% a past 6-month SA. Higher gender dysphoria, childhood physical and sexual violence, lifetime intimate partner violence, and mild or severe depression/anxiety symptoms were associated with increased lifetime SA risk (adjusted risk ratios [aRRs]=1.19-2.12, p < 0.05). Past 6-month SA was associated with high gender dysphoria, lack of health insurance, recent homelessness, childhood sexual violence, and severe depression/anxiety symptoms (aRRs=2.12-4.22, p < 0.05). Ages 31-40 years and college degree attainment were protective against lifetime SA. Findings underscore the importance of addressing early-life trauma and current structural vulnerabilities to reduce suicide risk among TGD adults.

Background:A decade of pre-exposure prophylaxis (PrEP) has lowered HIV incidence among men who have sex with men (MSM) but not enough to meet Ending the HIV Epidemic goals, and racial and ethnic disparities persist. The PrEP era has produced a population of former users facing lower barriers to restarting than PrEP-naive individuals. Reinitiation has not been treated as a distinct target. We aimed to compare its population-level impact with that of uptake and persistence. Methods:We used a network model of 100,000 cisgender MSM aged 15-65 in Boston, USA (21.5% Black, 18.9% Hispanic, 44.5% White, and 15.1% Other), parameterized with electronic health record data from 37,722 MSM (2012-2023) and calibrated to local surveillance. We compared 10-year population-wide and equity-focused (Black and Hispanic MSM) interventions scaling uptake, persistence, and reinitiation, reporting infections averted, number needed to treat (NNT), and disparities at comparison intensities, defined as multiples of the baseline reinitiation rate. Findings:A 2× reinitiation scale-up averted 15.8% of infections (1481; NNT 40) versus 10.0% for 2× uptake and 5.6% for maximum persistence; 5× reinitiation averted 32.6% at the same NNT. Equity-focused reinitiation produced the most favorable relative disparity patterns of the three levers, though inequities remained. Interpretation:Reinitiation was the most impactful PrEP continuum lever, a prevention-side analog of ART re-engagement warranting prospective evaluation. Restart can be supported with existing infrastructure, including EHR-triggered prompts at return encounters, and equity-focused implementation for Black and Hispanic MSM offers the most favorable disparity patterns. Funding:US National Institutes of Health and the Emory Center for AIDS Research.

Background Pre-exposure prophylaxis (PrEP) is effective in preventing HIV; however, syndemically linked psychosocial problems can contribute to adherence challenges. Objective The aim of this study is to test the efficacy of a stepped-care (text messaging, followed adherence counseling) PrEP intervention in men who have sex with men (cisgender or transgender) who are at risk for HIV acquisition and potentially PrEP non-adherence. Secondary and exploratory aims include examining mediators, moderators, and cost-effectiveness. Methods This 2-arm randomized controlled trial enrolled 300 men who have sex with men reporting at least one syndemically-linked psychosocial problem (e.g., polysubstance use, depression symptoms) prescribed PrEP. Recruitment sites in Miami, FL and Boston, MA equally randomized participants to standard care or the stepped-care intervention, which includes daily text message reminders, access to nurses, and, if continued non-adherence, four Life-Steps adherence counseling sessions (and two potential boosters). Study participation lasted 18 months with baseline and 6 quarterly assessment visits that included dried blood spot (DBS) testing for PrEP medication metabolites (TFV-DP) and self-reported adherence as primary outcomes. Results Participant related activities will be completed by July 2025. Conclusion We hypothesize that this ongoing study will demonstrate that participants will have better adherence over 18 months in the stepped-care / Life-Steps intervention relative to the standard of care condition. Positive outcomes from the present study may support an efficient model to deliver an effective adherence intervention to those with greater need.

PURPOSE:This study sought to identify latent classes of psychosocial adversity among men who have sex with men (MSM) who use stimulants, examine sociodemographic correlates of class membership, and assess differences in health service utilization across classes. METHODS:This secondary analysis used baseline data from 205 MSM who use stimulants in Boston, Massachusetts, and Miami, Florida (March 2018-March 2024). Latent class analysis was applied to identify patterns of psychosocial adversity based on childhood sexual abuse (CSA), four forms of interpersonal violence (IPV), and three types of sexual minority stress. Sociodemographic characteristics included age, sexual orientation, race and ethnicity, and socioeconomic status. Outcomes were binary (any/none) indicators of mental health care, substance use care, emergency department (ED) encounters, and inpatient admissions in the past 4 months. RESULTS:A three-class solution was selected: Low Psychosocial Adversity (n = 107; 52.2%), Past-Year IPV-sexual orientation discrimination (SOD; n = 56; 27.3%), and Prior IPV-CSA (n = 42; 20.5%). Lower socioeconomic status was associated with higher odds of membership in the Past-Year IPV-SOD class compared with the Low Psychosocial Adversity class (odds ratio = 2.30; 95% confidence interval = 1.04-5.23, P = 0.046). In exploratory pairwise comparisons, participants in the Prior IPV-CSA class had a higher prevalence of any ED encounters (47.6%) than those in the Low Psychosocial Adversity class (28.1%; χ2[1,204] = 4.44; P = 0.035). CONCLUSION:Among MSM who use stimulants, configurations of psychosocial adversity varied by sociodemographic context, with socioeconomic status distinguishing patterns of adversity, and showed limited differentiation in health service utilization. These findings underscore the role of structural conditions and support syndemic-informed, person-centered approaches to inform more equitable prevention and service strategies.

BACKGROUND:Data from randomized controlled trials of vitamin D3 supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse. OBJECTIVES:We evaluated the effect of vitamin D3 supplementation on healthcare utilization and other clinical outcomes among adults with coronavirus disease 2019 (COVID-19) and their close contacts. METHODS:We conducted a parallel 2-group randomized controlled double-blinded trial targeting free-living adults in the United States and Mongolia. Index participants with newly diagnosed COVID-19 were cluster-randomized with up to one of their cohabiting contacts either to an oral vitamin D3 loading dose of 9600 IU/d for 2 d followed by 3200 IU/d for 4 wk or to placebo. Participants completed weekly questionnaires on healthcare utilization, disease severity, and long COVID (index participants) or new SARS-CoV-2 infection (household contacts). The primary outcome was ≥1 healthcare visits (including hospitalization) or death within 4 wk among the index participants. RESULTS:Index participants (n = 1747) were a median of 38.0 y old (IQR: 31.1-47.0), 65.6% female/other sex, 4.2% Black non-Hispanic, 4.8% Hispanic/Latinx, 43.2% Asian, 44.3% non-Hispanic White, and 44.9% vitamin D deficient or insufficient (25-hydroxyvitamin D3 <20 ng/mL). Baseline characteristics for the household contacts (n = 277) were similar. The 4-wk cumulative incidence of healthcare utilization in index participants did not significantly differ between the vitamin D3 (n = 863) and placebo (n = 884) groups [cumulative incidences, 0.28 compared with 0.29; odds ratio (OR), 0.97; 95% confidence interval (CI): 0.75, 1.24]. Similar nonsignificant results were observed for the prespecified secondary treatment and prevention outcomes, though per-protocol analyses showed a nonsignificant trend toward benefit of vitamin D3 on the prevalence of long COVID at 8 wk (OR, 0.78; 95% CI: 0.59, 1.03). No safety concerns were identified. CONCLUSIONS:Among adults with newly diagnosed SARS-CoV-2 infections, vitamin D3 supplementation did not significantly change the 4-wk cumulative incidence of healthcare utilization or COVID-19-related outcomes compared with placebo. Promising results for long COVID warrant further study. This study was registered at clinicaltrials.gov as NCT04536298. First registered on 1 September, 2020.

BACKGROUND:Semaglutide, widely used for diabetes and obesity, has raised concerns about neuropsychiatric risks, including depression and suicidality. Given the high burden of depression among people with HIV (PWH), we assessed whether semaglutide initiation worsens depressive symptoms. METHODS:We conducted a within-person pre-post study of PWH initiating semaglutide at nine Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between April 2018 and October 2024. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) collected during routine care before and after semaglutide initiation. We estimated changes in PHQ-9 scores after semaglutide initiation using linear mixed models, overall and stratified by baseline depression severity (0-4 no/minimal, 5-9 mild, 10-14 moderate, and ≥15 moderately-severe to severe), body mass index (BMI), diabetes, and antidepressant use. RESULTS:Among 354 PWH (mean age 54; 77% male; 38% non-Hispanic White; 78% obesity; 60% diabetes), baseline PHQ-9 scores were 0-4 in 53%, 5-9 in 28%, 10-14 in 10%, and ≥15 in 9%. Semaglutide was not associated with overall changes in depressive symptoms (ΔPHQ-9 -0.1 [95% confidence interval (CI) -0.7, 0.5]). Scores increased slightly in those with no/minimal baseline depression (+1.2 [95% CI 0.5, 1.8]), were stable in mild/moderate depression, and decreased in moderately-severe to severe depression (-4.7 [95% CI -7.3, -2.2]). No worsening was observed across BMI, diabetes, or antidepressant subgroups. CONCLUSION:Semaglutide initiation was not associated with worsening depressive symptoms among PWH in care. While individual responses may vary, these findings add to evidence on semaglutide safety regarding mood in a high-risk population.

Objectives To understand the trade-offs between different statistical modeling approaches, using real world data with small sub-populations, with rare exposures and increasingly rare outcomes. In particular, to compare adjusted regression, inverse probability weighting, and matching. Methods Data for these analyses came from the RADAR (N=1,134) and combined CNICS/JHHCC (N=14,434) cohorts. We estimated prevalence ratios (PRs) for self-reported use of specific substances comparing subpopulations (SP), SP-1 vs SP-3 and SP-2 vs SP-3, where SP-1 was the largest proportion (92% in RADAR, 81% in CNICS/JHHCC), SP2 was moderate proportion (18% in CNICS/JHHCC) and SP-3 was the smallest proportion (8% in RADAR, 1% in CNICS/JHHCC) of the population. We calculated PRs using 1) unadjusted relative risk regression (RR); and adjusted estimates controlling for age, race/ethnicity, study site, and year of interview using: 2) standard adjustment in RR; 3) stabilized inverse probability of treatment weighting (IPTW); and 4) matching with up to 3 matches from SP-1 or SP-2 per SP-3 participant. Results For most substances, all methods yielded consistent estimates. There were large weights in some of the IPTW analyses and in three cases these resulted in substantially divergent estimates. For the comparison between SP-1 and SP-3, the estimate for smoking was 1.3-fold greater in the matched analysis (PR=1.33, 95% CI: 1.02-1.75) than in IPTW (PR=1.03, 95% CI: 0.78-1.37 ATE and PR=1.05, 95% CI: 0.88-1.26 ATT). Even more extreme divergence in estimates was observed for differences between SP-2 and SP-3 with respect to methamphetamine/amphetamine, (IPTW-ATE: PR=1.51, 95% CI: 0.79-2.89; IPTW-ATT: PR=2.36, 95% CI: 1.36-4.12); vs Matching: PR=2.71, 95%CI: 1.47-4.99) and cocaine (IPTW-ATE: PR=1.15, 95% CI: 0.55-2.38; IPTW-ATT: PR=1.81, 95% CI: 1.03-3.18); vs Matching: PR=1.38, 95%CI: 0.76-2.53). Conclusion The combination of a rare exposure and a rare outcome can produce challenges for commonly used confounding adjustment strategies, and it is often best to compare different modeling approaches to gain greater insight.

The United States Centers for Disease Control and Prevention recently released updated guidance on nonoccupational human immunodeficiency virus postexposure prophylaxis. The guidelines introduce coformulated antiretrovirals as a preferred regimen, which will likely positively impact prescribing practices and adherence. However, other barriers to access and uptake remain a challenge.

Little is known about Undetectable=Untransmittable (U = U) awareness among MSM in India. We analyzed baseline survey data from MSM (N = 1004) in an mHealth HIV testing trial in Mumbai and Thane, India. We assessed factors associated with U = U awareness and agreement (HIV treatment optimism) using multivariable Poisson regression. U = U awareness (29

BACKGROUND:Frailty occurs at younger ages among people with HIV (PWH) than those without HIV, but its impact on mortality is unknown. METHODS:We examined the association between frailty (defined by a validated phenotype including inactivity, fatigue, weight loss, and immobility) and mortality (ascertained from state and national death data) among PWH in the Centers for AIDS Research Network of Integrated Clinical Systems cohort between January 2015 and March 2024 using adjusted Cox proportional hazards models. RESULTS:Among 6750 PWH in this study, the average age was 50 years, 15% were female, 44% were prefrail, 11% were frail at baseline, and the incidence of frailty was 9.7 per 1000 person-years [95% Confidence Interval (CI):8.8 to 10.8] over an average of 5.5 years of follow-up. In adjusted models, frailty was associated with 2.7-times (95% CI: 2.0 to 3.6), and prefrailty with 1.5-times (95% CI: 1.2 to 2.0), higher risk of mortality. Prefrailty and frailty were consistently associated with an increased risk of death in models stratified by age (<50 vs. ≥50) and sex (male vs. female). Frailty was associated with 3.6-times (95% CI: 2.2 to 6.1) and 2.5-times (95% CI: 1.7 to 3.5) higher risk of mortality among PWH younger than 50 years and 50 years and older, respectively, and with 2.6-times (95% CI: 1.9 to 3.6) and 3.9-times (95% CI: 1.7 to 8.9) higher risk among male and female PWH, respectively. CONCLUSIONS:In a large cohort of PWH, frailty and prefrailty were associated with a greater risk of death among PWH of all ages. Preventing frailty in this high-risk population is an important public health priority.

Human immunodeficiency virus (HIV) remains an epidemic disproportionately affecting Black sexual minority men (BSMM). Prince George's County, Maryland, a majority-Black county, bears approximately three times the national prevalence and incidence of diagnosed HIV cases. Pre-Exposure Prophylaxis (PrEP) is extraordinarily effective for HIV prevention, yet uptake among BSMM remains low. We developed a community-based intervention for HIV-negative BSMM with sexual partners and no history of PrEP use in Prince George's County, Maryland. Study participants were recruited from January through March 2025 and followed for 6 months. Intervention activities were grounded in the MPowerment model and focused on increasing PrEP knowledge and acceptability, building social connection, and reducing internalized stigma related to race, sexuality, and PrEP. We tested for differences in PrEP use and each of these factors between intervention and control groups. We recruited 147 participants, with 126 (62 control, 64 intervention) followed at 6 months (85.7% retention). PrEP use at 6 months was 15.6% in the intervention group compared with 3.2% in the control group (RR = 4.84, 95%CI 1.11-21.23). The intervention group had significantly higher levels of PrEP knowledge, self-efficacy, resilience, and PrEP communication, and lower PrEP stigma, internalized homophobia, and internalized racism. Fidelity, activity participation, and participant satisfaction were high (>90%). Our intervention demonstrated a nearly 5-fold increase in PrEP use over 6 months compared with the control. The findings from our trial highlight the initial efficacy of culturally-tailored, peer-based interventions for BSMM. Participants found activities feasible, satisfactory, and effective. Additional and longer-term interventions may further improve PrEP uptake in this community.

OBJECTIVE:Patient-reported outcomes (PROs) provide important information to improve healthcare and facilitate research but can be difficult to implement in busy care settings. DESIGN:We integrated PRO collection into HIV care (2008-2024) with results summarized for providers to improve clinical care. METHODS:PWH presenting for HIV care at nine clinics across the United States in the CFAR Network of Integrated Clinical Systems (CNICS) were asked to complete a touch-screen-based PRO assessment at routine clinic visits using a web-based application. RESULTS:21 725 PWH completed the CNICS clinical PRO assessment 132 240 times (mean 6.1 assessments per PWH). Mean age at initial assessment was 43.8  years, 24.9% screened in for depression, 35.5% reported heavy episodic (binge) drinking, 38.9% smoking, 10.9% methamphetamine use, 11.7% recent intimate partner violence, and 8.4% reported unstable housing in the prior 30 days. DISCUSSION:We implemented a PRO assessment into HIV care at nine geographically dispersed clinics. PRO responses in domains known to drive adverse outcomes such as substance use were identified as were situational concerns such as unstable housing. This study demonstrated that use of a well designed PRO platform can address many of the barriers of paper and interview-based collection and be sustainable over time even as clinic flow and content priorities evolve. It demonstrated that PROs done for clinical care are useful to address clinically relevant research questions and institutional needs. Finally, this study demonstrated the feasibility of wide-spread implementation of a clinical PRO assessment into busy HIV clinical care settings with >130 000 assessments completed to date.

Abstract Over the past 15 years, there have been dramatic advances in HIV care, transforming HIV from a fatal illness to a manageable condition with people living with HIV (PLHIV) now living near normal lifespans. Modern antiretroviral therapy (ART) is highly effective, simple, and safe. Universal test-and-treat and immediate ART initiation is standard of care. The evolution of highly active antiretroviral therapy (HAART), now known as ART, over the past decade and a half has not only resulted in enormous benefit for PLHIV but has had a major impact on reducing the transmission of HIV when ART adherence is optimized. Treatment as prevention (TasP), referred to colloquially as undetectable equals untransmittable, or U=U, means that PLHIV who are on ART and achieve a durably undetectable viral load cannot sexually transmit HIV. Long-acting injectable antiretroviral drugs and other such future formulations are providing PLHIV with more ART dosing and delivery options. Equitable access remains a challenge.

Transgender men and transmasculine people who have sex with men (TMSM) are at elevated risk for HIV acquisition, have unmet HIV prevention needs, and have low uptake of antiretroviral pre-exposure prophylaxis (PrEP). To our knowledge, there are no published efficacious behavioral interventions to decrease HIV risk specifically for TMSM; this includes peer-delivered strategies that demonstrate high acceptability in this population. This paper describes the development, refinement, and optimization of theory-informed, peer-delivered digital interventions—which were feasible to implement and highly acceptable among the participant population—designed to increase PrEP uptake and adherence among adult transmasculine people who have sex with individuals assigned male at birth within the context of a full-scale, randomized factorial trial. Between March 2023-March 2025, we used an iterative community-engaged approach that included: (1) community and key stakeholder input, (2) theory- and evidence-informed manualized content with iterative refinement, (3) interventionist training and preparation, and (4) process evaluation and fidelity monitoring. Two theoretical frameworks and one theory of behavior change guided content development, structure, format and evaluation: The Healthcare Accessibility Framework, the Gender Affirmation Framework, and the Information, Motivation, and Behavioral Skills Model of behavior change. A 4-member Community Advisory Board of transmasculine individuals partnered with the research team to co-design interventions and study procedures. Additional input was obtained through one-on-one key stakeholder consultations with nine topic experts, clinicians, and community experts at partner organizations. Iterative refinement incorporated evidence synthesis, manual drafting, mock sessions, and structured feedback loops resulting in two refined virtually delivered interventions: (1) PrEP4T, a 6-session one-on-one peer navigation intervention (60-90 minutes/session) emphasizing goal setting, harm reduction, and supportive referrals; and (2) LS4TM, a 6-session peer-facilitated group-based behavioral intervention (2 hours/session), focusing on sexual health knowledge, gender affirmation, communication, and social support. A digital standard of care (SOC) resource guide of curated, gender-affirming sexual health, HIV prevention, and community resources was also developed. Interventionist training included approximately 15 hours of knowledge/skill building (asynchronous and live didactic sessions) and at least 12 hours of applied practice (mock sessions with structured feedback). Process evaluation and fidelity relied on participant- and interventionist-completed case reporting forms, reflecting community prioritization of interventionist and participant comfort during sessions. Key lessons learned included the importance of flexible, manualized intervention content structures that support fidelity while allowing personalized adaptation; using gender-affirming language through mirroring and dual phrasing; centering “voice” and “choice” in HIV prevention decision-making; incorporating behavior change scaffolding (e.g., goal setting, elicit-provide-elicit techniques); offering hands-on peer navigation and curated SOC resources to address structural access barriers; and leveraging digital tools to enhance engagement, shared learning, and community connection. Co-designing with transmasculine communities through an iterative, community-engaged development and refinement processes was essential for producing culturally responsive, theoretically-grounded, and gender-affirming HIV prevention interventions. Our findings can inform future peer-delivered and digital HIV prevention strategies tailored to the needs of specific populations, grounded in community partnerships and lived experience. ClinicalTrials.gov NCT06182280; https://clinicaltrials.gov/ct2/show/NCT06182280 RR2-10.2196/76831

Oral tenofovir is a key antiretroviral used for treatment and pre-exposure prophylaxis (PrEP) of human immunodeficiency virus (HIV). A gel form has been tested for vaginal and rectal PrEP. We have shown that 7 days of tenofovir 1% gel had broad-ranging effects on gene expression in the rectum, especially suppression of anti-inflammatory mediators and induction of cell proliferation. Similarly, oral PrEP induced type I/III interferon-stimulated genes in the gut. It is unknown how long these effects last and whether they occur in other relevant body compartments. We measured the transcriptomes and proteomes of tissue samples obtained before and after daily topical tenofovir 1% gel application for 14 days (Microbicide Trials Network [MTN]-014 trial, rectal and vaginal) or 56 days (MTN-017 trial, rectal). While many changes seen after 7 days diminish after 14 and 56 days, some remain, notably increases in cell proliferation- and type I/III interferon-related genes. Vaginal gel uniquely induces changes related to epithelial-mesenchymal transition and angiogenesis. Induction of type I/III interferon-related genes is the most consistent and persistent mucosal response to tenofovir, occurring after both oral and topical use and at all tested time points. Hypothetically, interferon induction could improve antiviral efficacy, but also contribute to an increased chronic disease burden in people with HIV.IMPORTANCEAnalyzing gene expression data from three separate clinical trials, we find that the antiretroviral drug tenofovir, which belongs to the class of nucleotide analogue reverse transcriptase inhibitors, induces the type I/III interferon system of innate immunity in the mucosa. This effect occurs in the absence of HIV infection and manifests itself over various treatment durations and after both oral and topical drug delivery. Tenofovir and other related medications are important components of long-term antiretroviral treatment taken by people living with HIV. Therefore, this unexpected immunological effect might need to be considered as a potential contributor to comorbidities in people living with HIV, as well as an immunopharmacological co-factor when testing novel HIV cure interventions.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT01768962, NCT01687218, and NCT01232803.

BACKGROUND:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are nephroprotective but are associated with early eGFR decline, also termed "eGFR dip." Despite elevated risk of kidney disease, this phenomenon is understudied among people with HIV (PWH). METHODS:In a 1:1 propensity score-matched cohort study using data from 9 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites, we compared new SGLT2i users with new users of other antihyperglycemic classes. We estimated adjusted hazard ratios (aHRs) for time to ≥10% and ≥30% eGFR decline using multivariable Cox proportional hazards models and analyzed eGFR change using multivariable linear mixed models. In addition, longer-term eGFR trends over 24 months were visualized using locally weighted scatterplot smoothing (LOWESS) curves. RESULTS:Among 1554 eligible PWH, we obtained 295 matched pairs. Over 6 months, eGFR decline incidence of ≥10% and ≥30% was higher among users of SGLT2i versus other antihyperglycemic classes (58.2% vs. 37.4%; aHR: 1.79; 95% CI: 1.40%-2.28%; and 17.3% vs. 9.8%; aHR: 1.69; 95% CI: 1.05-2.73; respectively). The adjusted mean eGFR change at 6 months was -2.62 mL/min/1.73 m 2 for SGLT2i versus 0.05 mL/min/1.73 m 2 for other classes. Long-term eGFR trends revealed an expected initial decline after SGLT2i initiation, followed by stabilization and a slower subsequent decline compared with other classes. CONCLUSIONS:Acute eGFR dips were more common among PWH initiating SGLT2i relative to other antihyperglycemic classes, although overall declines were small, transient, and consistent with the general population. Further research is needed to explore the long-term effects of SGLT2i in PWH.

Background:Internalized HIV stigma (IHS) is associated with reductions in antiretroviral therapy (ART) adherence and HIV viremia mediated through depression. However, there is still a need to quantify the direct impact of IHS on ART adherence to inform interventions to improve medication adherence.Methods:The Center for AIDS Research Network of Integrated Clinical Systems is a longitudinal, US-based, multisite cohort of people with HIV who complete patient-reported outcome assessments as part of HIV-care visits. Patient-reported outcome data include IHS items, ART adherence, depression assessments, substance use, and other outcomes. We examined associations between IHS and ART adherence using generalized linear latent and mixed models with a nonparametric random effects intercept to accommodate repeated measures. Results were compared with analyses using generalized estimating equations and marginal structural models.Results:Among 13,119 people with HIV, the mean age was 47.4 years, 17.6% were women, and 59.3% were non-White. Across 33,139 observations, controlled for repeated measures on individuals, HIV medication adherence was reduced by 1.07% for every point increase in IHS after controlling for age, sex, ethnicity, geographic location, and substance use, and 0.58% when additionally adjusted for depression score. Marginal structural models and generalized estimating equations provided similar results.Conclusions:Our study demonstrates that IHS has a direct association with reductions in ART adherence, which could affect other comorbid health outcomes that are influenced by unsuppressed viremia over time. Developing a thorough understanding of the mechanisms through which IHS affects ART adherence is critical for developing interventions to mitigate IHS and improve health outcomes across the lifespan.

BACKGROUND:We explored whether self-reported current cannabis use is associated with inflammatory biomarkers among people with HIV (PWH), given high rates of cannabis use and chronic immune activation among PWH. METHODS:At seven Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort sites, which integrate data on participant characteristics including demographic and clinical information, and substance use behaviors, we used linear regression to estimate the average difference in biomarkers associated with cannabis use, adjusted for demographic characteristics and sampling weights. Cannabis use was considered as Never, Former, or Current (past 3-month) use. Thirteen plasma biomarkers were measured once on or after 2010 among a subset of PWH on antiretroviral therapy with HIV viral suppression within CNICS. Cannabis use was assessed within 1 year prior to biomarker collection. Biomarkers were log-transformed and scaled by standard deviation to standardize estimates. RESULTS:Among 532 PWH, the average age at biomarker collection date was 47 years, 84% were male, 61% non-White, 30% reported current cannabis use, 35% former use, and 35% never using cannabis. In adjusted linear regression, current cannabis use was associated with higher soluble CD14 (sCD14) levels (β = 0.35; 95% confidence interval [CI]: 0.09, 0.61). Former cannabis use was associated with lower C-reactive protein (CRP) (β = -0.25; 95% CI: -0.47, -0.04), although current use was not (β = -0.25; 95% CI: -0.51, 0.01) compared to never use. CONCLUSIONS:Cannabis use may be related to lower CRP and elevated markers of microbial translocation (e.g., sCD14), which could have implications in increasing the risk of vascular events and should be investigated in a longitudinal setting.