CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

evidence for an age-by-sex interaction for 157 of all 363 proteins assessed (43%) after FDR correction. In those ≤47 years (Panel A), women had lower levels of largely immunoregulatory proteins than men, 4 of which were associated with higher mortality in the overall cohort. In contrast, in those >47 years, women had higher levels of predominantly inflammatory markers (36/42) than men, 26 of which were associated with higher mortality in the larger cohort (Panel B). Women also had lower levels of the immunoregulatory protein integrin beta 6 (which activates TGF-β1) than men regardless of age. Conclusion: The impact of sex on the plasma inflammatory proteome is highly dependent on age among ART-suppressed PWH, with women exhibiting more inflammation than men primarily at older ages. Whether menopause is responsible for unmasking these sex differences requires further study and is of high importance as many of these pathways are associated with increased mortality.

therapy (ART) causes an increase in naïve and central memory cells that have longer telomeres, leading to an overall BTL increase. However, tenofovir (TDF/ TAF) and abacavir (ABC), which are potent inhibitors of human telomerase activity, have been shown to negatively affect the BTL increase. We investigated the effect on BTL over 96 weeks after starting a dual therapy (DT) with dolutegravir (DTG) plus lamivudine (3TC) vs a standard triple therapy (TT) with an anchor drug plus two NRTIs, one of which was TDF/TAF or ABC. Methods: In this prospective longitudinal study we enrolled ART-naïve PLWH who started DT or TT, with no current AIDS event. We assessed BTL by monochrome multiplex qPCR (expressed as telomere to single-copy gene ratio, T/S) at the time of ART initiation (baseline, BL), virological success (VS) (achievement of HIV-RNA<50cps/mL), and at weeks 48 (W48) and 96 (W96). We used an adjusted mixed model (GLM) to evaluate the effects of both the between- and within-subject factors. Linear regressions were performed to identify the variables associated with BL BTL and BTL changes over W96. Results: From 2018-2022 we enrolled 71 participants: 41 in the TT and 30 in the DT group (Table1). Compared to TT, participants in DT were younger and with higher CD4 count. However, the two groups showed comparable BL HIV-RNA and HIV-DNA load, they similarly reached VS within 2 months and maintained viral suppression over the follow-up. At BL, the medians (IQR) of BTL were similar in the TT and DT groups: 0.93 (0.79-1.09) and 1.06 (0.84-1.19) (p=0.103). Overall, BTL increased over time, showing a similar trend in both groups (p=0.769); specifically, we observed no variation up to W48 (+0.02, p=0.803) and a significant mean gain at W96 (+0.11, p=0.015). BL BTL was associated with younger age (-0.07 per 10 yr. increase; -0.11/-0.02; p=0.004). Higher BTL change was associated with shorter BL BTL (-0.90; -1.20/-0.60; p<0.001). Conclusion: In this setting, ART-naïve PLWH who initiated either DT or TT showed a similar evolution of BTL over time. They did not show any significant change in BTL after 1-year follow-up,. However, a gain was observed at W96, suggesting a beneficial effect of ART, regardless of triple or dual regimen use. Rebecca Abelman 1 , Samuel R. Schnittman 2 , Gabriele B. Beck-Engeser 1 , Noah Aquino 1 , Gabrielle C. Ambayec 1 , Carl Grunfeld 1 , Edward Cachay 3 , Joseph J. Eron 4 , Michael S. Saag 5 , Robin M. Nance 6 , Joseph A. Delaney 6 , Heidi M. Crane 6 , Adam Olshen 1 , Peter W. Hunt 1 , for the CFAR Network of Integrated Clinical Systems (CNICS) Group 1 University of California San Francisco, San Francisco, CA, USA, 2 Massachusetts General Hospital, Boston, MA, USA, 3 University of California San Diego, La Jolla, CA, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 University of Alabama at Birmingham, Birmingham, AL, USA, 6 University of Washington, Seattle, WA, USA Background: Among ART-suppressed people with HIV (PWH), women have higher levels of several plasma inflammatory markers than men, but the effect of sex on the larger plasma inflammatory proteome, and whether these differences are modified by age, remains unclear. Methods: We analyzed 363 unique plasma proteins (Olink Inflammation Explore panel) within a randomly sampled sub-cohort of ART-suppressed (<400 copies HIV RNA/mL) CNICS participants. The relationship between natal sex and plasma proteins was assessed with linear regression models adjusted for age, natal sex, nadir CD4, site, race, MSM status, and clinical factors (smoking, IDU, HCV history, ASCVD risk score). Age-sex interaction terms were also assessed, stratifying age above and below the median age of 47, which in prior studies has approximated the average age of menopause in women with HIV. Mortality was separately assessed in Cox proportional hazards models adjusted for VACS index and site. All p-values were adjusted for multiple comparisons by controlling for the false discovery rate (FDR) using the Benjamini-Hochberg method. Results: Of the 922 ART-suppressed participants sampled, 103 died over a median follow-up of 9 years. Median age was 47; 162 (18%) were female. Median current and nadir CD4 count were 579 cells/mm 3 and 245 cells/mm 3 , respectively, with a median ART duration of 5 years. A large number of sex differences in inflammatory markers were identified along with significant Age Modifies the Association Between Sex and the Plasma Inflammatory Proteome in Treated HIV

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Consequences of Low-Level Viremia by Sex Among People With HIV in the United States Amalia Aldredge 1 , Cyra C. Mehta 1 , Cecile D. Lahiri 1 , Maria L. Alcaide 2 , Kathryn Anastos 3 , Todd T. Brown 4 , Audrey L. French 5 , Frank Palella 6 , Michael Schneider 7 , Phyllis Tien 8 , Anandi N. Sheth 1 , Lauren F. Collins 1 1 Emory University, Atlanta, GA, USA, 2 University of Miami, Miami, FL, USA, 3 Albert Einstein College of Medicine, Bronx, NY, USA, 4 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 Stroger Hospital of Cook County, Chicago, IL, USA, 6 Northwestern University, Chicago, IL, USA, 7 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 8 University of California San Francisco, San Francisco, CA, USA Background: Low-level viremia (LLV) is common in people with HIV (PWH) receiving antiretroviral therapy (ART) and has been associated with adverse outcomes including virologic failure (VF), drug resistance, and non-AIDS comorbidities (NACM). As differences in these outcomes have been observed in men versus women with HIV, we investigated the effect of LLV on these outcomes by sex. Methods: We included men enrolled in the Multicenter AIDS Cohort Study (MACS) and women in the Women's Interagency HIV Study (WIHS) from 2003 2020 who reported ART use for ≥1 year with ≥2 consecutive HIV-1 viral loads (VL) <200 c/mL. PWH were then categorized using 4 consecutive VL results (baseline period) as: virologic suppression (VS; all VL below lower limit of assay detection), intermittent LLV (iLLV; non-consecutive detected VL <200 c/mL), persistent LLV (pLLV; ≥2 consecutive detected VL <200 c/mL), or VF (any VL ≥200 c/mL). Outcomes were assessed from after baseline period through 5 years. Those with baseline VF were excluded. At first visit after baseline period, PWH with multimorbidity (≥2 of 5 NACM: hypertension, dyslipidemia, diabetes, cardiovascular disease, kidney disease) were excluded from that analysis. Adjusted Cox proportional hazards models estimated the association of virologic category with time to incident a) VF and b) multimorbidity. Results: Of 2,395 PWH, 67% were women, median age was 48 years, 53% were Black, 20% were Hispanic, median CD4 count was 616 cells/µL, and 89% reported ≥95% ART adherence. Over the baseline period (median 1.5 years), VS, iLLV, and pLLV occurred in 61%, 18%, and 6%, respectively. Among 1968 and 1123 PWH included in each analysis, incident VF and multimorbidity occurred in 25% and 21%, respectively. Compared to PWH with VS, the adjusted hazard ratio (aHR) for incident VF in women was 1.8 (95% CI 1.4,2.4) for iLLV and 2.4 (1.5,3.6) for pLLV, while in men was 1.4 (0.9,2.3) for iLLV and 3.1 (1.7,5.6) for pLLV (LLV*sex interaction p=0.4). Compared to PWH with VS, the aHR for incident multimorbidity in women was 0.9 (0.6,1.3) for iLLV and 1.7 (1.0,2.9) for pLLV, while in men was 1.4 (0.9,2.4) for iLLV and 0.7 (0.2,1.9) for pLLV (LLV*sex interaction p=0.1) (Table). Conclusion: In a diverse cohort of US PWH, LLV was associated with an increased risk of developing VF, regardless of sex. There was a trend toward pLLV

Poster Abstracts

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