Frank Joseph Palella

Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH), particularly in women with HIV (WWH), but underlying mechanisms remain unclear. We used longitudinal untargeted metabolomics to identify metabolic signatures of INSTI-related weight gain in WWH. We analyzed serum from 192 participants in the Women's Interagency HIV Study: 38 virologically suppressed WWH who initiated INSTIs (INSTI group), 88 virologically suppressed WWH who remained on their original antiretroviral therapy (non-INSTI group), and 66 women without HIV (WWoH). Samples were collected at baseline (6-12 months before INSTI initiation), 1-6 months post-initiation, and 1-2 years post-initiation, with matched visits for controls. High-resolution metabolomics was performed by liquid chromatography-mass spectrometry. Within each group, linear mixed-effects models adjusted for baseline age and BMI compared longitudinal metabolite changes between weight gainers and maintainers, and significant features were analyzed by Mummichog v2.0 pathway enrichment. Mean age was 45.7 ± 8.9 years and mean BMI 32.4 ± 8.3 kg/m2, with no differences across groups; within each group, gainers and maintainers were demographically comparable (p > 0.05). In the INSTI group, metabolites differentiating gainers from maintainers were enriched in 16 pathways across timepoints, predominantly lipid-related (56%), including the polyunsaturated fatty acid (PUFA) pathways linoleic acid and arachidonic acid metabolism. In the non-INSTI and WWoH groups, differentiating metabolites spanned a broader range of pathways, including amino acid metabolism. Weight gain among INSTI-treated WWH is characterized by a distinct, lipid- and PUFA-dominated metabolic profile, providing mechanistic insight that may inform therapeutic strategies.

Background: The COVID-19 pandemic prompted an abrupt transition to telemedicine for HIV care, necessitating the exploration of provider attitudes and experiences to understand its ongoing viability and impact. Objective: This study aimed to assess providers’ attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic at 2 time points and at 2 clinical sites. Methods: We conducted a convergent mixed methods study to evaluate and explore providers’ attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic, applying the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and the updated Consolidated Framework for Implementation Research. This study assessed HIV providers via surveys at 2 time points, capturing responses on the acceptability, appropriateness, feasibility, and maintenance of telemedicine. Semistructured key informant interviews were conducted on a random selection of 10 participants to explore perceived experiences with telemedicine. Results: Among emailed providers, 43 of 83 (51.8%) and 27 of 82 (32.9%) responded to survey 1 and survey 2, respectively. The first survey recorded telemedicine usage at 75%, which decreased to 58% by the second survey. Overall, the majority of respondents agreed with statements that assessed telemedicine as appropriate, acceptable, and feasible. There were overall few statistical differences in responses between sites, although more providers at the community site indicated at least some potential value in telemedicine when compared to providers at the university hospital (100% agree or strongly agree vs 82.3%; P =.04) in survey 1. In survey 1, providers with more than 10 years of experience were less likely to report telemedicine helped them see more patients (31.6% agree or strongly agree vs 70.6% for providers with ≤10 y of experience; P =.008). Fewer experienced providers felt they could talk about private issues with their patients during telemedicine (57.9% of more experienced vs 88.3% of less experienced providers; P =.03). Key informant interviews provided qualitative insights into telemedicine integration, revealing mixed sentiments; providers appreciated the flexibility and accessibility that telemedicine offered but preferred in-person visits for their thoroughness, especially for physical examinations and laboratory tests. Despite initial barriers such as technical challenges and patient preferences for in-person visits, telemedicine was deemed feasible for maintaining communication and care quality. Providers highlighted the need for better technological support and ongoing training to optimize telemedicine usage. Conclusions: Our study underscores telemedicine as a sustainable adjunct to traditional HIV care, emphasizing the importance of addressing technological and training barriers to enhance its efficacy.

Background: Macrophages play an important role in kidney inflammation and fibrosis. Circulating biomarkers of macrophage activation are elevated in people with HIV (PWH). We therefore determined their associations with kidney function and chronic kidney disease (CKD) risk in people with and without HIV. Methods: We analyzed data from 2 prospective cohorts: the Women's Interagency HIV Study and Multicenter AIDS Cohort Study. Serum concentrations of soluble (s)CD14, sCD163, galectin-3 (Gal-3) and Gal-3 binding protein (Gal-3BP) were measured between 2004 and 2006. We examined each biomarker's association with estimated glomerular filtration rate (eGFR) using multivariable linear regression and with incident CKD (2 consecutive eGFR <60 mL/min/1.73 m2) using cause-specific Cox proportional hazards models, adjusting for sociodemographics, CKD risk factors, and HIV-related factors. Results: Among 1284 participants, 61% were women, 70% were PWH, of whom 59% were virally suppressed (HIV RNA < 200 copies/mL); median eGFR was 93 mL/min/1.73 m2 at baseline. All macrophage biomarker concentrations were higher in PWH versus without HIV (P < .05). Cross-sectionally, higher concentrations of sCD14 and Gal-3 were independently associated with lower eGFR (P < .001). Over a median follow-up of 14.2 years, incident CKD occurred in 23% of PWH and in 11% without HIV. Each standard deviation higher concentration of sCD14 and Gal-3BP was independently associated with 22% and 29% increased CKD risk, respectively. Associations for sCD163 and Gal-3 were attenuated after multivariable adjustment. Findings were similar in analyses restricted to PWH. Conclusions: Macrophage activation may mark and/or contribute to CKD development. Studies are needed to determine whether targeting immune activation improves kidney health in PWH.

Background: People with human immunodeficiency virus (HIV; PWH) are at increased risk of hepatitis C virus (HCV) coinfection and experiencing negative clinical outcomes. We evaluated direct-acting antiviral (DAA) initiation among PWH with HCV to identify factors associated with initiation. Methods: US and Canadian PWH ≥18 years with a detectable HCV RNA in the North American AIDS Cohort Collaboration on Research and Design were followed up from the latest of first detectable HCV viremia, antiretroviral therapy initiation, enrollment date, or 1 January 2014 until the first of DAA prescription, clearance of HCV viremia, loss to follow-up, death, or 31 December 2021. We estimated the cumulative incidence of DAA initiation accounting for the competing risks of death and HCV viral clearance. Cox proportional hazard models estimated crude and adjusted hazard ratios and 95% confidence intervals to identify factors associated with DAA initiation. Results: Among 6300 PWH with a detectable HCV RNA, 3672 (58%) initiated DAA. Accounting for the competing risks of death and HCV clearance, by 8 years after study entry 6% of eligible PWH had not initiated DAA. A lower rate of DAA initiation was identified among non-Hispanic black and Hispanic PWH compared with non-Hispanic white PWH. DAA initiation was lower among PWH reporting injection drug use as their HIV acquisition risk, at-risk alcohol use, smoking, detectable HIV viremia, or a history of AIDS. A higher Fibrosis-4 score was associated with increased DAA initiation. Conclusions: The DAA initiation gap among PWH engaged in care and eligible for treatment has greatly narrowed over time. Targeted approaches to increase equity in DAA initiation are needed to eliminate HCV among PWH.

Background: Sex-specific, long-term, body weight change in persons with human immunodeficiency virus (PWH) following switch to regimens containing integrase strand transfer inhibitors (INSTIs) is unknown. Methods: We compared PWH enrolled in the MACS/WIHS Combined Cohort Study (2007–2020) who switched/added an INSTI to their antiretroviral therapy (ART) regimen to those remaining on non-INSTI ART and to people without human immunodeficiency virus (PWOH), by sex. Follow-up time was time since switch visit (or comparable visit in controls). Linear regression mixed-effects models assessed the effects of sex, group, and time upon weight and anthropometric measurements. Results: Of 3464 participants included, women (411 INSTI, 709 non-INSTI, 818 PWOH) compared to men (223 INSTI, 412 non-INSTI, 891 PWOH) were younger (47.2 vs 54.5 years), were majority non-Hispanic Black (65% vs 23%), and had higher mean body mass index (31.5 vs 26.9 kg/m2), respectively. Women switching to INSTIs experienced greater absolute and percentage weight gain compared to men at 5 years: +3.0 kg (95% confidence interval [CI], 2.1–3.9) versus +1.8 kg (95% CI, .7–2.9) and +4.6% (95% CI, 3.5%–5.7%) versus +2.3% (95% CI, 1.0%–3.6%), respectively ([sex × time × group interaction, P < .01). Compared to men, women switching to INSTIs experienced greater hip and thigh circumference gain at 5 years: +2.6 cm (95% CI, 1.6–3.6) versus +1.2 cm (95% CI, .3–2.1) and +1.5 cm (95% CI, .7–2.2) versus −0.2 cm (95% CI, −.9 to .5), respectively. Conclusions: Weight change among PWH over 5 years after switch to INSTI was 2-fold higher in women than men. The cardiometabolic implications of this difference in weight gain remain unknown.

Purpose Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Methods Adult TW on GAHT (n=29) were recruited for a cross-sectional study (2018-2020). Cisgender men (CM, n=48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results Overall, median age was 53 years and BMI 29 kg/m²; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusions Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Supplemental Figure 3: Effect of age on prevalent (SF3a) incident (SF3b) infections.

Supplemental Figure 2: Clearance of prevalent (panel A) and incident (panel B) oral HPV16 infections over 10 years

Supplemental Figure 4: Effect of sex on prevalent (SF4a) incident (SF4b) infections.

Supplemental Figure 6: Effect of HIV and CD4 on prevalent (SF6a) incident (SF6b) infections.