BACKGROUND: Despite availability of evidence-based alcohol reduction interventions (EBIs), unhealthy alcohol use (UAU) remains a barrier to HIV medication adherence, viral suppression, and retention in HIV care. While translation of alcohol EBIs into HIV clinical practice is important for comprehensive HIV care, their implementation in HIV settings is impeded by resource constraints, workflow challenges, and negative perceptions of alcohol-related care. METHODS: Guided by the Consolidated Framework for Implementation Research and Reach, Effectiveness, Adoption, Implementation and Maintenance frameworks, we will conduct a Hybrid Type 3 effectiveness-implementation study testing whether external practice facilitation increases reach, adoption, implementation, and maintenance of stepped care for UAU in three Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) HIV clinics in the United States. We will secondarily test whether practice facilitation is associated with clinical outcomes. We will first conduct a mixed methods formative evaluation to tailor delivery of practice facilitation (including the tools, technical assistance, and content expertise offered) based on each site’s context and needs (Aim 1). We will then deliver practice facilitation across the three sites sequentially to implement a stepped-care model of alcohol treatment to patients with UAU. Stepped care, where non-responders to alcohol EBIs are offered a more intensive therapy, will specifically include person- or computer-delivered brief alcohol intervention, on-line cognitive behavioral therapy, and linkages to alcohol pharmacotherapy. Clinical outcomes will include: (1) clinic-level implementation outcomes of stepped care EBIs for alcohol use including reach, adoption, maintenance, using mixed methods (Aim 2a) and (2) patient-level outcomes using interrupted time series analysis with synthetic controls (Aim 2b). Finally, we will use summative evaluation to describe barriers and facilitators to implementation of the interventions at each site to describe maintenance and inform widespread sustainable implementation (Aim 3). DISCUSSION: This trial tests an implementation strategy to improve the delivery of stepped care, an evidence-based treatment approach for UAU in HIV clinics. Practice facilitation has shown promise for implementing evidence-based care for UAU in primary care but use of practice facilitation for this purpose in HIV clinics is novel. Results from this implementation study may support broader implementation of alcohol evidence-based practices in HIV care. TRIAL REGISTRATION: The trial is registered with Clinicaltrials.gov, identifier NCT05241990 Date of submission 2/16/2022.

Background and aims:People with HIV (PWH) experience a persistent symptom burden that negatively affects quality of life and daily functioning. Evidence examining modifiable lifestyle behaviors that may mitigate symptoms is limited. We examined longitudinal associations between objectively measured physical activity, diet quality, and symptom burden in PWH. Methods:PROSPER-HIV enrolled adults with well-controlled HIV receiving care at four Centers for AIDS Research Network of Integrated Clinical Systems sites in the United States. Participants completed annual assessments, including physical activity levels using actigraphy, dietary intake measured with three 24-h recalls generating the Healthy Eating Index-2015 (HEI-2015), and symptom burden with the HIV Symptom Index. Linear mixed models evaluated associations adjusting for age, sex at birth, race/ethnicity, and site. Results:Among 704 participants (mean age, 52.7 years; 78% male; 52% non-Hispanic Black), symptom burden remained stable over follow-up. Participants averaged 5426 ± 3149 steps/day, 164 (IQR, 67-311) minutes/week of moderate-to-vigorous physical activity (MVPA), and an HEI-2015 score of 48.1 ± 14.6. The most prevalent bothersome symptoms were muscle aches/joint pain, fatigue, sleep disturbance, anxiety, and trouble remembering. More steps/day were associated with fewer bothersome symptoms (β = -0.59 steps; P < .01), whereas more sedentary time was associated with higher symptom burden (β = 0.64; P < .01). Higher diet quality was associated with lower symptom burden (β = -0.20; P = .01). Duration of MVPA and light physical activity were not associated with symptom burden. Conclusions:Among adults with well-controlled HIV, a higher daily step count, less sedentary time, and better diet quality were associated with lower symptom burden, highlighting critical lifestyle behaviors to support symptom management in HIV care. Learning points:Among adults with well - controlled HIV, objectively measured higher daily steps and better diet quality, but not weekly moderate - to - vigorous physical activity, were associated with lower symptom burden over three years. Achievable targets to improve persistent, clinically meaningful symptoms in HIV care were identified. Clinical trial registration number:ClinicalTrials.gov [NCT03790501].

BACKGROUND:People with HIV disproportionately experience homelessness and other forms of housing instability. Understanding how housing status influences HIV clinical outcomes remains limited, especially among individuals engaged in care. METHODS:We evaluated associations between housing status and HIV care markers using clinical data and patient-reported measures from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort of adults receiving HIV care across the US, between 2019-2025. We used relative risk regression and linear regression to estimate associations between self-perceived housing instability and outcomes including HIV viral suppression (<200 copies/mL), self-reported antiretroviral therapy (ART) use and adherence (visual analog scale), and CD4 cell count, adjusted for demographic characteristics, year, and site. RESULTS:Among 6,873 individuals in clinical care, nearly 10% reported some form of housing instability at their most recent visit: 4.6% "Unstable," 3.3% "Homeless," and 1.7% "Don't know." Compared to stably housed individuals, the prevalence of viral suppression was lower among those experiencing homelessness (PR=0.82, 95% CI: 0.77-0.89) and unstable housing (PR=0.94, 95% CI: 0.90-0.98), as was the prevalence of ART use, mean ART adherence, and mean CD4 count. Results were similar when stratified by substance use and depression and when compared to a community-based cohort of people with HIV. CONCLUSION:Housing instability is associated with a lower prevalence of HIV viral suppression even among individuals engaged in clinical care. These results highlight lack of access to stable housing as a structural barrier to successful management of HIV and to ending the HIV epidemic in the US.

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.

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.

ABSTRACT:People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH. Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009-2020), we assessed the association between cannabis use and VTE risk. Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57-1.07) nor current (aHR 0.74, 95% CI 0.51-1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE. Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE. Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.

Background:Antiretroviral therapy (ART) has revolutionized the clinical management of people with human immunodeficiency virus (HIV), transforming HIV infection into a chronic condition. Yet, the mechanisms of action and off-target effects of modern combination ART regimens versus individual ART medications are not fully understood. Methods:Using the L1000 assay, we profiled transcriptional responses to 11 single ART drugs and 6 ART combination regimens across three human cell lines, HepPG2 (liver), HK2 (kidney), and THP-1 (monocyte). Differentially expressed genes were analyzed against host-HIV protein-protein interactions (PPIs) and genes implicated in ART-associated side effects. Results:Across all cell types, ART combination regimens induced distinct transcriptional profiles compared with their component drugs. Combinations more strongly perturbed genes encoding proteins involved in HIV-host PPIs, consistent with their enhanced antiviral efficacy. Transcriptional responses also recapitulated known ART-induced adverse effects related to dyslipidemia, altered body composition, and renal impairment. Combination regimens were less coupled to these gene signatures, suggesting mechanisms that may underlie their improved safety profiles. Several genes and pathways were consistently modulated across treatments: ACTG1, or actin gamma 1 - a gene that encodes gamma actin, a protein crucial for the localization of the HIV reverse transcription complex, was downregulated in four combination regimens, while ORM2, Orosomucoid 2, upregulation emerged as a common response to individual drugs. ACTG1 was previously found to be downregulated in ART naïve people living with HIV who naturally control HIV replication, suggesting its role as a candidate host mediator. To facilitate data exploration, we developed ARTexpress, an interactive portal enabling visualization of gene expression changes before and after ART exposure across all three cell lines. Conclusion:ART regimens affected transcriptional signatures of genes involved in HIV-host PPIs and were less tied to common ART-related side effects. Our findings support the use of high-throughput transcriptomics to detect specific mechanisms of ART on- and off-target effects to help prioritize new drug targets and compounds in future development and optimization of safer and more efficient ART.

Comparing ActiGraph Low-Frequency Extension (LFE) vs. normal filters on accelerometer-derived physical activity and sedentary behavior in 492 people with HIV. Participants wore ActiGraph 7-10 days; metrics (sedentary bouts, light physical activity, MVPA, steps) analyzed with both filters using Wilcoxon and Quade's ANCOVA. LFE increased MVPA (213.5 vs. 162.4 min/week) and steps (11 239 vs. 4853/day; P < 0.001) with minimal effects on sedentary bouts/light physical activity; effects were consistent across subgroups, indicating caution when comparing studies with different filters.

OBJECTIVE:To assess outcomes of heavily treatment experienced people with HIV (PWH) who received the antiretroviral therapy salvage regimen containing raltegravir, etravirine, and darunavir/ritonavir (known as TRIO). METHODS:Data were from the ART Cohort Collaboration, which is a collaboration of European and North American HIV cohort studies. Adult PWH were eligible if they had a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors; three or more primary protease inhibitor and nucleoside reverse transcriptase inhibitor mutations; three or fewer darunavir and nonnucleoside reverse-transcriptase inhibitor mutations; received TRIO between 2007 and 2018; virologic failure at TRIO start; and did not receive any TRIO drugs previously. Follow-up began at TRIO start. We examined rates of virologic suppression on TRIO, AIDS/death, receipt of drug-reducing regimens post-TRIO in those virologically suppressed, and subsequent virologic response. We used a competing risks framework to estimate 5-y cumulative incidence of outcomes. RESULTS:Among 126 eligible PWH, 24% were female, and median age was 46 y (IQR: 41-50). Median follow-up was 7.9 y (IQR: 5.1-9.3). A total of 94 (74.6%) were virologically suppressed on TRIO. Of these, 26 (28%) subsequently switched to a drug-reducing regimen, of whom 19 of 26 (73.1%) were virologically suppressed at their next viral load measure. The 5-y cumulative incidence of outcomes was stop TRIO and start another three or more drug regimen (39.1%); simplify (16.0%); stop TRIO without switching (8.8%); and death on TRIO (7.2%). CONCLUSIONS:Although the most common outcome after TRIO was switch to another three or more drug regimen, almost one third of virologically suppressed PWH under TRIO (with a history of multidrug resistance) switched to a drug-reducing regimen, the majority of whom maintained suppression.

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.

Background Despite the recognition of substance use and sex work as public health issues, the intersection of these areas, especially within the rural US, is an area of special importance.Methods The Rural Opioid Initiative comprises of eight research cohorts spanning 10 states and 65 rural US counties. Between 1/2018-3/2020, individuals who reported past 30-day substance injection or opioid misuse were recruited. Analyses were restricted to people who use drugs (PWUD) who reported trading "vaginal or anal sex for drugs, money, housing, or other things you need" in the past 30 days. We analyzed cross-sectional associations between injection drug use and sexual behaviors associated with hepatitis C virus (HCV)/HIV infection transmission, access to harm reduction, and HCV status among PWUD and engaged in sex work in rural US areas.Results Of the 2045 participants, 9% (n=180) reported engagement with sex work, with just over half being women (58% [n=104]). In adjusted models, people who engaged in sex work, compared to PWUD who did not, had higher prevalence ratios of past 30-day receptive syringe sharing (adjusted prevalence ratio [aPR]=1.69, 95% Confidence Interval [95%CI]=1.44-1.98), practice of multiple injections per injection episode (aPR = 1.28, 95% CI = 1.15-1.43), practice of syringe mediated drug sharing (aPR=1.50, 95% CI=1.32-1.71), condomless sex (aPR=1.62, 95% CI=1.48-1.77) and condomless sex with someone who injects drugs (aPR=2.05, 95% CI=1.76-2.39). PWUD engaged in sex work were less likely to report easy condom access (aPR=0.88, 95% CI=0.80-0.96), while no significant differences were observed for most other harm reduction access measures.Conclusion PWUD engaged in sex work in the rural US had higher likelihood of injection drug use and sexual behaviors associated with HCV/HIV infection transmission, while having lower use of and access to condoms. This study emphasizes the importance of ensuring affordable access to condoms within the context of harm reduction services, especially given the limited access to health care and supportive services, particularly in rural communities.

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.

Background: We examined associations between physical activity (PA), muscle function, and sarcopenia in older people with HIV (PWH). Setting: Multi-site PROSPER-HIV Study, including data from Seattle, WA, Cleveland, OH, and Birmingham, AL. Methods: In this cross-sectional study, we analyzed data from 148 PWH aged ≥50 years. Assessments included dual-energy X-ray absorptiometry for lean mass, handgrip strength, gait speed, chair stands, and Short Physical Performance Battery (SPPB). PA was objectively measured with ActiGraph accelerometers. Sarcopenia was defined using EWGSOP2, SDOC, and SDOC-HIV criteria. Regression models assessed associations between PA and sarcopenia, adjusting for age, sex, race, and body mass index. Results: Participants were 62.5 years old on average and 29.1% female. Sarcopenia prevalence varied widely: 1.4% under EWGSOP2, 4.1% under SDOC, and 15.2% under SDOC-HIV, with poor agreement across definitions (κ≤0.16). Participants presented a median of 105 minutes/week of moderate-to-vigorous PA (MVPA) and 4,123 steps/day. Higher MVPA was associated with lower odds of probable/confirmed sarcopenia using EWGSOP2 (OR=0.982; p <0.01). No significant associations were observed using SDOC or SDOC-HIV definitions (all p >0.05). MVPA was positively associated ( p <0.05) with handgrip strength and SPPB. Our fully adjusted model indicated that approximately 83 additional minutes of MVPA per week would be required to increase handgrip strength by 1 kg. Conclusion: Higher MVPA was associated with better muscle strength and physical performance, and with lower odds of probable/confirmed sarcopenia using EWGSOP2, whereas no significant associations were observed using SDOC or SDOC-HIV. These findings support further investigation of MVPA as a potentially important lifestyle strategy for maintaining muscle health in older PWH.

ABSTRACT:People with HIV (PWH) have a high prevalence of obstructive sleep apnea (OSA), yet the condition receives minimal attention despite a high prevalence of OSA risk factors. PWH attending HIV care between 2008 and 2023 were eligible. Sleep studies were identified in electronic health records. We estimated associations between completion of a study and HIV factors and fatigue using adjusted relative risk regression. Among 3,977 PWH, 4% completed a sleep study. PWH who underwent sleep studies were older (50 vs. 48 years), fewer had low current CD4 cell counts (2% vs. 11% < 200 cells/mm3), and more had HIV viral suppression (97% vs. 85%) than those who did not. Bothersome fatigue was associated with 2.9 times (95% confidence interval: 1.9-4.4) greater likelihood of completing a sleep study. Sleep studies are rarely conducted among PWH. PWH who received a sleep study had better HIV control (higher CD4 count/viral suppression) and a greater burden of fatigue and OSA-related comorbidities.

BACKGROUND:Psychological distress (eg, depression) and social stressors (eg, HIV-related stigma) can affect HIV-related outcomes such as antiretroviral therapy adherence and health-related quality of life (HRQL). Limited research on adverse childhood experiences such as childhood household violence (CHV) has shown a similar impact on HIV-related outcomes, particularly virologic suppression, although little is known about mediating pathways with factors such as psychological distress and social stressors. SETTING:Data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort were analyzed. This article examines the relationship between CHV and HIV-related outcomes, and potential differences between those with and without CHV by age (<50 vs. ≥50 years). METHODS:Bivariate comparisons, linear regressions, and mediation analyses between CHV and other variables were used to assess association with outcome measures. RESULTS:Among 7705 people with HIV, CHV was reported by 19% (n = 1498). CHV was associated with lower antiretroviral therapy adherence (P < 0.001), more HIV symptoms (P < 0.001), and lower HRQL (P < 0.001). In addition, CHV exposure was associated with worse depressive symptoms (P < 0.001), increased panic symptoms (P < 0.001), lower social support (P < 0.001), greater self-report of HIV stigma (P < 0.001), and more exposure to intimate partner violence (P < 0.001). Psychological distress and social stressors mediated the relationship between CHV and adherence, HIV symptoms, and HRQL, with depressive and panic symptoms accounting for the greatest proportion mediated. CONCLUSIONS:CHV has an adverse impact on social and psychological factors in adulthood for people with HIV. Depressive symptoms and panic symptoms are potential targets for interventions.

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.

BACKGROUND:Implementation of long-acting cabotegravir/rilpivirine (LA-CAB/RPV) has been challenging and may limit its uptake. We describe the number of people with HIV (PWH) prescribed LA-CAB/RPV at 9 US academic HIV clinics in the Center for AIDS Research Network of Integrated Clinical Systems and clinic-level variation in LA-CAB/RPV prescriptions. METHODS:Using a sequential explanatory mixed methods design, we analyzed clinical cohort data of PWH prescribed LA-CAB/RPV, then conducted key informant surveys to ascertain each clinic's Exploration-Preparation-Implementation-Sustainment phase in conjunction with implementation determinants mapped to the Consolidated Framework for Implementation Research. We stratified the cohort analysis by phase. RESULTS:Between 21-Jan-2021 and 30-Sep-2024, 1,451 (6%) of 22,379 PWH in care were prescribed LA-CAB/RPV. Among those prescribed, 15% had baseline viral load ≥200 copies/mL (200/1,451). Two sustainment-phase clinics that experienced fewer insurance-related barriers, planned prior to LA-CAB/RPV availability, had a pharmacy team coordinating LA-CAB/RPV services, and customized the electronic health record (EHR) system to track insurance approvals and/or injection appointments prescribed LA-CAB/RPV to 16% (924/5,638) of PWH in care. Four sustainment-phase clinics that had a mix of payor coverage and insurance plans, and adequate staffing prescribed to 3% (213/8,154). Three implementation-phase clinics with difficulty procuring LA-CAB/RPV due to restrictive insurance coverage and/or hospital policy and staffing challenges prescribed to 4% (314/8,587). CONCLUSIONS:Barriers related to insurance coverage and drug procurement impacted the number of PWH prescribed LA-CAB/RPV as did processes to plan for, and adapt to, these barriers. Scale-up efforts should consider team coordination and EHR-facilitated tracking to support the growing number of PWH on LA-CAB/RPV.