Background: Direct oral anticoagulants such as rivaroxaban are a feasible and convenient option for anticoagulation in people living with HIV. Here, we assess the effect of cobicistat or darunavir/cobicistat on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of rivaroxaban. Methods: This open-label, fixed sequence, intrasubject drug-drug interaction PK study enrolled healthy participants who received oral study drugs sequentially as follows: rivaroxaban 10 mg once on day 1, cobicistat 150 mg once-daily on days 2 to 7, rivaroxaban 10 mg once on day 7, darunavir/cobicistat 800/150 mg once-daily on days 8 to 13 followed by rivaroxaban 10 mg once on day 13. Serial PK and PD plasma samples were obtained on days 1, 7, and 13 over 24 hours. Safety was assessed throughout the study. Results: Twelve participants enrolled and completed three phases of the study. Rivaroxaban geometric mean ratios (GMR, rivaroxaban + cobicistat versus rivaroxaban alone) and 90% confidence interval (CI) for C max and AUC 0-∞ were 1.50 (1.10-1.90) and 2.14 (1.70-2.58), respectively. Rivaroxaban GMR (rivaroxaban + darunavir/cobicistat versus rivaroxaban alone) and 90% CI for C max and AUC 0-∞ were 1.53 (1.13-1.94) and 2.12 (1.68-2.56), respectively. Rivaroxaban concentrations were positively correlated with PD markers in a linear fashion and returned to near-baseline 24 hours post-dose. All adverse events were mild to moderate in severity and resolved by the end of the study. Conclusion: Coadministration of cobicistat and cobicistat-boosted darunavir with rivaroxaban resulted in a clinically significant increase in rivaroxaban drug exposure. Further study can inform safety and efficacy of rivaroxaban dose reduction.
Background: In the US, the Veterans Health Administration is the largest single institutional provider of Human Immunodeficiency Virus (HIV) care for veterans. Retention in care can affect treatment adherence and care outcomes. Psychiatric disorders are prevalent in people with HIV and may lead to poorer retention in care and outcomes. Objectives: To examine the association between retention in HIV care, psychiatric comorbidities, and clinical outcomes among veterans with HIV. Research Design: In this retrospective study, veterans aged ≥18, seen with a diagnosis of HIV between 2000 and 2017, were identified from the Corporate Data Warehouse. We identified those with and without psychiatric comorbidities in the HIV cohort. Outcomes (mortality, viral suppression, and inpatient and outpatient visits) were assessed over a five-year follow-up period. Retention in care was measured during the first year of follow-up. We modeled outcomes as a function of retention in care and tested the moderating effects of psychiatric comorbidity and treatment for psychiatric comorbidity. Results: Cohort consisted of 59,649 veterans with a diagnosis of HIV; 66% had psychiatric comorbidity, and 90% received treatment for it. Overall, 49% were retained in HIV care. Retention in care was associated with better survival and viral suppression, regardless of psychiatric comorbidity; however, psychiatric comorbidity influenced healthcare utilization. Conclusions: Our study provides important insights into the relationship between retention in care, psychiatric comorbidity, and outcomes in veterans with HIV. Future research must assess the barriers to care and strategies to integrate mental health and HIV treatments for veterans.
INTRODUCTION:Steatotic liver disease (SLD) is highly prevalent in people with HIV (PWH) and is a major cause of morbidity and mortality in this population. However, it remains unclear whether SLD is influenced by HIV infection and whether the clinical management of PWH who have SLD should differ from non-HIV populations. METHODS:Liver steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) among 1,580 women (1,117 with HIV; 463 without) enrolled in the Women's Interagency HIV Study between 2013 and 2018. Steatosis was defined by a controlled attenuation parameter (CAP) ≥248 dB/m, and clinically significant fibrosis by liver stiffness ≥7.1 kPa. Participants were classified according to the AASLD diagnostic algorithm for SLD. Differences in fibrosis prevalence by HIV status were evaluated, and multivariable logistic regression was performed to identify factors associated with SLD and fibrosis, adjusting for age, ethnicity, BMI, alcohol use, diabetes, and smoking. RESULTS:Prevalence of SLD was 740 of 1580 (47%) and did not differ by HIV serostatus. Most SLD was metabolic dysfunction-associated steatotic liver disease (MASLD; 629 of 740 [82%]). HIV infection was associated with higher odds of clinically significant fibrosis only among women with SLD (adjusted OR 1.48, 95% CI 1.01-2.16, p=0.04; HIV*SLD interaction among entire cohort p=0.03). DISCUSSION:In this study, most SLD in women living with HIV is classified as MASLD. HIV infection is associated with higher odds of hepatic fibrosis only among those with SLD. Further work is needed to understand how HIV may potentiate fibrosis in the setting of SLD.
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:Long-acting injectable antiretroviral therapy (LA-ART) has enormous potential benefit for increasing viral suppression among persons with HIV (PWH). SETTING:U.S. HIV care facilities. METHODS:We analyzed data on past 12-month LA-ART prescriptions collected over 3 annual data collection cycles (2021-2023) from probability samples of U.S. adults with HIV (collected 6/1/2021-5/30/2024, N=11,524). We report weighted percentages of PWH prescribed LA-ART and use prevalence ratios (PRs) with predicted marginal means and 95% confidence intervals (CIs) to quantify differences in prescription of LA-ART over time and between groups. RESULTS:The percentage of PWH prescribed LA-ART increased from 0.4% (CI 0.2-0.7) in the 2021 cycle to 3.4% (CI 2.8-3.9) in the 2023 cycle (PR 7.8 [CI 4.5-13.6]). During the 2022-2023 cycles, prescription of LA-ART was higher among those living in Northeastern Medical Monitoring Project (MMP) states versus Southern MMP states (3.4% [CI 2.4-4.3] vs. 1.9% [CI 1.3-2.5], PR 1.8 [1.2-2.8]) and those receiving care at Ryan White HIV/AIDS program (RWHAP)-funded versus non-funded facilities (2.9% [CI 2.4-3.4] vs. 1.8% [CI 1.3-2.4], PR 1.6 [CI 1.1-2.2]). Older age (>50 vs. <40 years) was also associated with lower ART prescription. CONCLUSION:Prescription of LA-ART is increasing among U.S. adults with HIV, though prevalence remains low. LA-ART uptake lagged in the South, where HIV infections and negative health outcomes are disproportionately high. Comprehensive HIV care delivery-such as found in RWHAP-facilities-may facilitate LA-ART adoption.
BACKGROUND:Arts-based sexual health workshops may improve adolescent sexual health, yet limited studies have evaluated outcome trends over time. This study examined HIV prevention outcomes before and after school-based workshop participation among adolescents in the Northwest Territories (NWT), Canada. METHODS:We analyzed seven waves of pretest and immediate posttest data from adolescents aged 13-18 years in 17 NWT communities from 2018-2019 to 2024-2025. Surveys assessed sociodemographic characteristics, HIV knowledge, and condom use self-efficacy (CUSE). Paired-samples t-tests examined pretest to posttest differences. Mixed-effects linear regression models examined trends in change scores across school years and adjusted for the number of previously completed arts-based sexual health workshops. RESULTS:The pretest sample included 1,936 workshop observations; 1,579 had paired outcome data. Mean age was 13.64 years (SD=1.47); 48.86% were cisgender girls, 19.62% identified as lesbian, gay, bisexual, or queer, 70.05% identified as Indigenous, and 68.16% lived outside of Yellowknife in rural settings. HIV knowledge increased from 2.74 (SD=3.13) to 8.05 (SD=4.18), with a large effect size (Cohen's dz=1.30). CUSE increased from 19.59 (SD=4.40) to 20.32 (SD=4.70), with a small effect size (Cohen's dz=0.15). HIV knowledge gains increased across school years, particularly among older adolescents and cisgender girls. CUSE gains also increased; no sociodemographic interaction was statistically significant. CONCLUSION:Arts-based sexual health workshop participation was associated with immediate improvements in HIV knowledge and CUSE across seven school years among Northern and Indigenous adolescents in the NWT. Findings support continued evaluation of culturally responsive, arts-based HIV prevention in Northern and remote settings.
Background: Little is known of condom use self-efficacy (CUSE) trajectories over time and associations with HIV prevention engagement. We examined longitudinal associations between CUSE trajectories and HIV prevention engagement, and the mediating role of HIV-related stigma, among urban refugee youth in Kampala, Uganda. Methods: This cohort study with refugee youth in Kampala collected data at three timepoints from 2022 to 2024. We conducted latent class growth analysis (LCGA) to identify distinct CUSE trajectories over time. We then conducted path analysis to explore associations between CUSE trajectory classes and HIV prevention engagement (lifetime HIV/ STI testing, HIV self-testing [HIV-ST] uptake and awareness, recent condom use), examining the mediating role of HIV-related stigma. Results: We included 176 participants (mean age: 21.0, standard deviation: 2.5; 51.7% women, 48.3% men) with 520 observations. Two latent CUSE trajectories were identified: persistently high (n=451; 86.7%) and sustained low (n=69; 13.3%). In the direct effect model, higher CUSE trajectory scores were associated with increased lifetime STI testing, HIV-ST uptake and awareness, and recent condom use. In the indirect effect model including HIV-related stigma: a) HIV-related stigma partially mediated the associations between the high CUSE trajectory and lifetime STI testing, and b) HIV-related stigma was associated with reduced HIV-ST uptake and awareness and reduced recent condom use, even in the high CUSE trajectory class. Conclusions: Higher CUSE trajectories were associated with improved HIV prevention engagement, yet HIV-related stigma attenuated these associations. While CUSE is important for HIV prevention agency, sustained attention to HIV-related stigma reduction is necessary.
Background: Weight gain in people with HIV (PWH) has generated concern regarding metabolic consequences of antiretroviral therapy (ART). It is unclear whether weight gain differs between virally suppressed (VS) PWH and people without HIV (PWoH) when accounting for key characteristics, or which clinical and demographic factors drive weight gain in VS PWH. Methods: This retrospective observational cohort study utilized electronic records from 12 US federally qualified health centers (January 2015-August 2023). Part A employed multi-stage propensity score matching (4:1 ratio) to compare 3-year weight trajectories adjusting for demographics, comorbidities, and medications. Part B used classification and regression trees (CART), logistic regression to identify predictors of weight gain (≥10% gain with BMI shift or baseline obesity) vs minimal gain (>0% to <5%) among 10,413 suppressed PWH. Results: In matched, adjusted analyses (1,296 VS PWH; 4,168 matched PWoH), no significant difference in mean 3-year weight change was observed between VS PWH and PWoH (0.4 kg, 95% CI: -0.1 to +0.9). A higher proportion of VS PWH gained ≥10% of baseline weight compared to PWoH (15% vs. 11%, p<0.001) and increased BMI shifts (13% vs. 11%, p=0.02). Among virally suppressed PWH, significant gain correlated with younger age (median 44 vs. 51 years), female sex (28% vs. 16%), Black race (49% vs. 37%), and lower baseline BMI. No ART regimen were associated with significant weight gain . Conclusion: Weight change in suppressed PWH are similar to those of matched PWoH. Clinical and sociodemographic characteristics, not ART regimens, correlated with 3-year gain in VS PWH.
Background: Criminal legal involved (CLI) persons who use drugs (PWUD) are at high risk of exposure to HIV, yet few initiate pre-exposure prophylaxis (PrEP). Understanding interest in PrEP and the different formulations of PrEP may improve uptake in this population. Methods: Participants were CLI adults aged 18 or older, used opioids and/ stimulants, tested negative for HIV and met CDC PrEP eligibility criteria. Characteristics of persons interested in PrEP were compared to those who were not interested in PrEP at baseline. Among those interested in PrEP, characteristics were compared for those who preferred long-acting injectable (LAI) versus oral PrEP. Results: Of 566 persons enrolled, 35.1% (N=199) were interested in PrEP; of those, 60.8% (N=121) preferred LAI vs 39.1% (N=78) oral PrEP. PrEP interest was greater in persons from Texas (50%) vs Connecticut (18.3%). A significantly higher odds of being interested in PrEP was associated with having a methamphetamine use disorder and a higher self-perceived risk of HIV; and a history of sharing IDU equipment was associated with a higher odds of being interested in LAI vs. oral PrEP. Conclusions: Among CLI PWUD eligible for PrEP, persons in TX, were more interested in PrEP compared to persons in CT. Persons with a methamphetamine use disorder and a higher self-perceived risk of HIV were predictors of PrEP interest and sharing IDU equipment was a predictor of interest in LAI vs. oral PrEP. More research on patient choice and shared decision making should be included to improve PrEP initiation.
BACKGROUND:Ensuring culturally responsive HIV testing is essential to advancing the goals of the Ending the HIV Epidemic (EHE) initiative, particularly among young sexual minority men (YSMM), who continue to experience disproportionate HIV incidence. METHODS:We conducted a youth-led mystery shopping study across six Florida counties between 2023 and 2025 to assess the quality of publicly funded HIV Counseling, Testing, and Referral (CTR) services. Using a validated assessment tool, trained YSMM completed 301 visits and evaluated site-level performance across ten domains. RESULTS:While many sites demonstrated strengths in provider respect, visual inclusion, and PrEP information, consistent deficits emerged in safer sex counseling, relationship-centered dialogue, and medical form inclusivity across the state. CONCLUSIONS:Youth-led mystery shopping captured experiential aspects of service quality often missed by traditional metrics and surfaced actionable gaps in prevention counseling. Our findings offer a rigorous diagnostic of Florida's HIV prevention infrastructure, underscoring how community-engaged quality assurance methods might be embedded in EHE strategies to ensure services are accessible, affirming and effective for those most at risk.
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.
BACKGROUND:Event-driven preexposure prophylaxis/PrEP (EDP), or PrEP taken around the time of sex, could be a preferred option over daily PrEP among cisgender gay, bisexual, and other men who have sex with men (MSM). However, recommendations for EDP versus daily dosing require consideration of optimal strategies for HIV prevention based on heterogeneous behavioral and biological PrEP indications. METHODS:We used network-based mathematical HIV transmission modeling to understand the potential population-level impact of implementing EDP alongside daily PrEP using the 2-1-1 dosing schedule: 2 pills on the day of sex, 1 pill a day after, and 1 pill 2 days after. We simulated HIV transmission among 100,000 MSM in Atlanta, Georgia over 10 years. Compared to a baseline scenario with only daily PrEP and no EDP, we tested counterfactual scenarios that increased EDP use by changing initiation rates, expanding EDP to MSM not indicated for daily PrEP, and targeting EDP among MSM with low daily PrEP adherence who discontinued daily PrEP. RESULTS:Increasing EDP initiation such that overall PrEP use was nearly double that at baseline (28.5% vs. 16.1%) yielded a percent of infections averted (PIA) of 18.3%. Expanding eligibility for EDP to any sexually active MSM resulted in a PIA of 15.8%. Targeting EDP for MSM discontinuing PrEP did not yield population-level improvements. Increasing initiation of EDP had a greater impact on PIA compared to improving EDP adherence. CONCLUSIONS:Using EDP to improve overall PrEP use resulted in reductions in HIV incidence, while targeted EDP initiation for MSM with low daily PrEP adherence did not improve outcomes over 10 years.
BACKGROUND:Unhealthy alcohol use contributes to poor HIV-related outcomes. Alcohol under-reporting may be associated with HIV viral non-suppression and all-cause mortality risk, especially at the high end of the spectrum. We evaluated whether alcohol under-reporting was associated with these outcomes among PWH with unhealthy alcohol use who were receiving ART. METHODS:We pooled data from six studies of PWH in Uganda (ADEPT-T, DIPT, Extend), United States (MWCCS), and Russia (Russia ARCH 1, St Peter). We included PWH on ART who engaged in unhealthy drinking as determined by the alcohol biomarker phosphatidylethanol (PEth)≥50ng/mL. Self-reported alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). We defined under-reporting of high-risk alcohol use as PEth≥200ng/mL and AUDIT-C score<6, and examined HIV viral non-suppression (≥200copies/mL or limit of assay detection) and an all-cause mortality risk score (Veterans Aging Cohort Study [VACS] Index 1.0) as outcomes. We explored level of -under-reporting of alcohol use using a continuous variable. RESULTS:In our sample of 1,435 PWH with unhealthy drinking, 24% under-reported high-risk alcohol use (prevalence range 1-34% across studies). We observed positive, non-significant associations between under-reporting of high-risk alcohol use and viral non-suppression and all-cause mortality risk score. An exploratory continuous under-reporting variable was significantly positively associated with all-cause mortality risk. CONCLUSIONS:Our findings indicate that under-reporting of high-risk alcohol use is common among PWH and suggest that under-reporting of alcohol use may mask other health issues, as reflected by increased mortality index scores. Low-cost methods to improve alcohol use are needed.
Introduction: Nineteen percent of new HIV diagnoses in the United States in 2022 occurred in women. One barrier to HIV prevention is low perception of possibility of infection. We explored the qualitative data on perception of chances of HIV infection in women to elucidate how women conceive potential for infection. Methods: Included articles were published between 2014 and 2024 with information on women, HIV, and perception of potential for infection. The codebook was created from emerging and theoretical constructs. Articles were coded using Dedoose. Codes were reviewed for cross-cutting themes and summaries created. Confidence in review findings was assessed with the CERQual approach. Results: The meta-synthesis included twenty papers. These included four papers focused on women engaged in substance use and five focused on Black individuals. Four themes emerged: women controlled aspects of their lives and altered possible exposures with the use of condoms or needle exchange programs, women knew they could not control all their potential exposures, misinformation and incomplete information affected women’s ability to assess their exposures, and perceptions of potential for infection were dynamic and dependent on current priorities in their lives. Conclusions: Women assessed their possibility for HIV based on their perception of control, their access to information, and based on life circumstances. Understanding how women think about their potential for infection can allow healthcare professionals to better counsel women on their chances of HIV transmission, leading to greater HIV prevention.
Background: The 2013 HIV Organ Policy Equity Act facilitated HIV-to-HIV organ transplants, enabling people with HIV to receive transplants more quickly. However, managing drug interactions between ART and immunosuppressive regimens remains a challenge. Objective: This study assesses the safety and effectiveness of cabotegravir/rilpivirine (CAB/RPV), an injectable ART, in maintaining HIV virologic suppression in kidney and liver transplant recipients. Methods: A retrospective review of three clinical studies evaluated CAB/RPV in transplant recipients with HIV. Participants had suppressed HIV RNA levels before transplant and were monitored post-transplant every six months. Results: Nine transplant recipients (7 kidney, 2 liver) received CAB/RPV. All maintained HIV suppression, with no allograft loss, although one liver recipient experienced acute rejection. One participant died from trauma unrelated to the transplant or HIV. Conclusion: CAB/RPV shows promise for HIV management after transplantation. Further research is needed using a larger cohort.
BACKGROUND:People with HIV (PWH) experience excess cardiovascular disease (CVD) risk with persistent inflammation considered a key driver, despite antiretroviral therapy (ART). Low-level viraemia (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 viraemia despite ART use. METHODS:We conducted a cross-sectional sub-study within the South African UTRA trial (NCT05333679). Endothelial function was measured with EndoPAT using the natural log-transformed reactive hyperaemia 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 (AUC). Body-mass index (BMI), waist-to-hip ratio (WHR), and body roundness index (BRI) were modelled 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 CVD risk. Median LnRHI was 0.69 (IQR 0.50-0.94). Mean cumulative VL AUC was 1.55 log10 copy-years/mL (IQR 1.30-2.20), consistent with LLV. Cumulative VL was not associated with endothelial function after adjustment. In contrast, LnRHI varied significantly and non-linearly across BMI, WHR, and BRI, 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 adds 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.
BACKGROUND:Adolescents and young adults living with HIV (AYAHIV) aged 15-24 years experience poorer HIV outcomes than other age groups, with frequent interruptions from care. Interruptions during the first year of antiretroviral therapy (ART) are especially concerning, as they occur before sustained viral suppression. We estimated the incidence of early HIV care interruption and associated factors among AYAHIV initiating ART in the Khayelitsha cohort, Western Cape, South Africa. METHODS:We conducted a retrospective cohort study of AYAHIV initiating ART between 2017 and 2021. Early HIV care interruption was defined as ≥90 days late for a scheduled refill without documented death or transfer. Participants were followed for 12-15 months. Cox proportional hazards models assessed associated factors, adjusting for age, sex, calendar year, dispensing interval (single-month vs multi-month), and regimen among 2020-2021 initiators. A sensitivity analysis was restricted to those with ≥4 refills. RESULTS:Among 5,149 AYAHIV (85% female; median age 23 years), 44% experienced early interruption, most within six months. Initiation in 2020 (adjusted Hazard ratio (aHR): 1.10, 95% confidence interval (95% CI): 1.03, 1.17) and 2021 (aHR: 1.28 95% CI: 1.18, 1.39) was associated with increased interruption risk versus 2017-2019. Dolutegravir was associated with a reduced risk compared to efavirenz (aHR: 0.87 95% CI: 0.78, 0.97). In sensitivity analyses (n=3,013), 32% interrupted, with similar associations. CONCLUSIONS:Early HIV care interruption was common, particularly during COVID-19. Dolutegravir was associated with improved retention, yet substantial early interruptions persisted, highlighting the need for intensified youth-focused support following ART initiation.
BACKGROUND:To better understand HIV and cardiovascular disease (CVD) effects on brain white matter during HIV infection, advanced diffusion imaging and comprehensive predictor analyses are essential. SETTING:Prospective observational cohort study. METHOD:84 virally suppressed people with HIV infection (PWH) and 48 uninfected controls underwent T1-weighted, FLAIR, and diffusion MRI at baseline and 24 months later (75 PWH and 40 controls). White Matter Hyperintensity (WMH) volumes were derived from structural scans. Fixel-based analysis tract-based metrics included fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC). RESULTS:Relative to controls, mixed models showed significant reductions (p<.05 - p<.01) of FC, and lower FDC to a lesser extent, in multiple long cortical association tracts, and within striatal- and thalamic-frontoparietal connections in PWH at both time points. Higher CVD risk was associated with reduced FC in the arcuate fasciculus and FDC in the cingulate gyrus (p<.05). In PWH, more severe cognitive impairment and longer duration of HIV disease was associated with worse FDC across multiple tracts (p<.03 - p<.001). Lower baseline CD4 counts was associated with lower FD in the frontal association tracts (p<.05 - p<.005). Higher WMH volume was associated with higher CVD risk (periventricular p<.001, deep p<.03), but not HIV status. CONCLUSIONS:Major brain white matter tracts are impacted by HIV status, HIV duration, cognitive impairment, baseline CD4, and CVD risk to a lesser extent, despite equal WMH burden between infection groups. Our study provides further evidence of active immuno-vascular underpinning of HIV neuropathogenesis on fine white matter structure despite controlled HIV.
BACKGROUND:The HIV Prevention Trials Network 094 INTEGRA study sought to fill the gap in implementation science literature by exploring the delivery of integrated prevention and care for HIV and opioid use dependence (OUD) through mobile units to people who inject drugs (PWID). SETTING:Five U.S. INTEGRA sites with diverse implementation landscapes disproportionately affected by the HIV and opioid epidemics (New York, Philadelphia, Washington, DC, Houston, Los Angeles) . METHODS:In-depth qualitative interviews from an embedded implementation science evaluation were conducted with 37 clinical and research INTEGRA staff delivering integrated care through mobile units. Pragmatic qualitative analysis was guided by the PRISM framework to identify key implementation needs, challenges, and solutions for delivering the INTEGRA intervention via mobile units in local neighborhoods. RESULTS:Staff described how mobile delivery of INTEGRA reduced key barriers that limit PWID access to HIV and OUD services. Yet, they also detailed complex implementation needs, including the proactive coordination among staff to ensure sustained access to INTEGRA services, navigating internal and external spaces to deliver services, maintenance-related demands to keep the mobile unit's infrastructure operational, and interdependent efforts that bridged the mobile unit's service delivery within the extant health systems and community landscapes. CONCLUSION:Findings demonstrated that mobile integrated care models can reduce access barriers for PWID but require tailored implementation strategies to address operational, spatial, infrastructural, and community-level demands. Results may help inform an implementation blueprint for similar communities working to respond to the intersecting HIV and opioid epidemics affecting PWID across U.S. settings.
BACKGROUND:People with HIV (PWH) are living longer due to effective antiretroviral therapy (ART) but face accelerated aging, accumulating comorbidities, and high rates of polypharmacy. Whether neuroinflammatory biomarkers are associated with polypharmacy and adverse clinical outcomes such as falls in this population is unknown. METHODS:We performed a cross-sectional analysis of baseline data from 600 virally suppressed PWH ≥40 years enrolled in the ACTG A5322 HAILO cohort. Plasma neurofilament light chain (NfL), neopterin, and soluble CD14 (sCD14) were measured. Multivariable logistic regression examined associations between each biomarker and polypharmacy (five or more non-ART medications), recurrent falls (two or more falls/6 months), and slow gait speed less than one m/s), adjusting for age, sex, and comorbidity burden. RESULTS:The median age was 54 years, 78% of participants were male, and 232 participants (39%) had polypharmacy. Elevated NfL was independently associated with polypharmacy in multivariable analysis (aOR 1.16 [95% CI 1.07-1.26]). In the total population, elevated NfL (OR 1.24 [1.05-1.46]) and sCD14 (OR 1.12 [1.01-1.23]) were each associated with recurrent falls. Among participants with polypharmacy, only elevated sCD14 remained associated with recurrent falls on stratified multivariable analysis (OR 1.15 [1.02-1.30]). No biomarker was significantly associated with slow gait speed. CONCLUSIONS:In older virally suppressed PWH, plasma NfL and sCD14 are associated with distinct adverse clinical phenotypes-medication burden and fall risk, respectively, and may serve as complementary biomarkers of distinct biological pathways relevant to aging in HIV.
