CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

182

Letermovir for CMV Suppression Improves Immunologic and Functional Aging Outcomes in Treated HIV Sara Gianella Weibel 1 , Kristine M. Erlandson 2 , Doug Kitch 3 , Shirley Qiu 4 , Yoshi Fukazawa 5 , Milenka V. Meneses 1 , Scott L. Letendre 1 , Michael P. Dube 6 , Lawrence Fox 7 , John Koethe 8 , Priscilla Hsue 9 , Davey Smith 1 , Michael L. Freeman 10 , Peter W. Hunt 5 , for the ACTG A5383 Study Team 1 University of California San Diego, La Jolla, CA, USA, 2 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Harvard University, Cambridge, MA, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 AIDS Healthcare Foundation, Los Angeles, CA, USA, 7 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 8 Vanderbilt University Medical Center, Nashville, TN, USA, 9 University of California Los Angeles, Los Angeles, CA, USA, 10 Case Western Reserve University, Cleveland, OH, USA Background: People with HIV (PWH) and CMV face an increased risk of frailty and aging-related outcomes, yet the causal role of CMV remains untested. Methods: A randomized trial assessed whether 48 weeks of letermovir, a CMV terminase inhibitor, reduced plasma sTNFR2 levels (primary endpoint) and other immunologic and functional aging-related outcomes in PWH seropositive for CMV on suppressive ART, compared to ART alone. Randomization was stratified by CD4 count (50% with <350 cells/mm³) and sex at birth (>30% female identity). A planned futility analysis was conducted after 40 participants (of a planned 180) reached week 8. Linear mixed models evaluated continuous outcome changes between arms. Results: As previously reported, the trial stopped early as the futility analysis showed unexpected increases in sTNFR2 at week 8 in the letermovir arm (n=18) compared to the control arm (n=21). However, from weeks 8 to 48, sTNFR2 levels declined significantly in the letermovir arm (P=0.001), such that the reduction from baseline at week 48 was nominally greater in the letermovir than control arm (diff: -9%, P=0.20). IL-6 also transiently increased at week 8 (+27%, P=0.02) then declined by week 48 (-28%, P=0.003) in the letermovir arm. IL-6R and IL1b levels declined to a greater degree in the letermovir arm throughout the treatment period (diff: -10%, P<0.001 and -29%, P=0.005). At week 48, the letermovir arm had greater declines in CMV-specific IgG titers (-28%,P<0.001) and CD8 counts (-119 cells/mm 3 ,P=0.024), and greater CD4/CD8 ratio increases (+14%,P=0.008, Panel A ). By week 48, chair rise time improved by a mean -1.7 seconds (-15%) in the letermovir arm (P=0.002) and to a greater degree than the control arm (P=0.02, Panel B ). Improved chair rise performance at week 48 was associated with reductions in IL1b (ρ=0.45, P=0.023) and IL6R (ρ=0.44, P=0.026), and increases in the CD4/CD8 ratio (ρ=-0.67, P<0.001). Although not statistically significant, other functional outcomes like grip strength, gait speed, and Fried frailty classification showed trends favoring letermovir. Conclusions: Letermovir initially increased some inflammatory markers but ultimately resulted in sustained reductions in inflammation, improved CD4/ CD8 ratios, and enhanced physical function/leg strength in PWH with CMV on suppressive ART. These findings suggest that suppression of asymptomatic CMV with a CMV-specific inhibitor may improve aging-related outcomes. Larger studies are needed to establish the clinical significance of these results.

183

Preliminary Efficacy for HPTN 094: 26-Week RCT of Integrated Strategies for People Who Inject Drugs Philip Andrew 1 , Nabila El-Bassel 2 , Steve Shoptaw 3 , Brett S. Hanscom 4 , David Goodman-Meza 5 , Irene Kuo 6 , Jordan E. Lake 7 , Ellen Morrison 8 , Jayla Harris 1 , Timothy Skalland 4 , Paul Richardson 9 , Melissa Cummings 10 , Dale Burwen 11 , Redonna Chandler 12 , David Metzger 13 , for the HPTN 094 Study Team 1 Family Health International 360, Durham, NC, USA, 2 Columbia University, New York, NY, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 Fred Hutchinson Cancer Center, Seattle, WA, USA, 5 Kirby Institute, Sydney, Australia, 6 The George Washington University, Washington, DC, USA, 7 University of Texas Health Science Center at Houston, Houston, TX, USA, 8 ICAP at Columbia University, New York, NY, USA, 9 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 10 Statistical Center for HIV Research and Prevention, Seattle, WA, USA, 11 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 12 National Institute on Drug Abuse, Rockville, MD, USA, 13 University of Pennsylvania, Philadelphia, PA, USA Background: People who inject drugs (PWID) face high morbidity and mortality from addiction and HIV. This abstract reports findings from HPTN 094 on whether 26 weeks of “one stop” integrated health services delivered in a mobile unit, supported by peer navigation, improves use of MOUD, increases viral suppression among people with HIV (PWH), and increases use of pre-exposure prophylaxis (PrEP) among people without HIV (PWOH) compared to 26 weeks of peer navigation to local services. Methods: HPTN 094 is a 26-week, HIV serostatus-neutral, randomized controlled trial with follow-up through 52 weeks conducted in Houston, Los Angeles, New York, Philadelphia, and Washington DC. Study arms: Experimental: Integrated services delivered in a mobile unit with peer navigation and transition to local services at 26 weeks; Active control: Peer navigation to existing local services throughout. Integrated services were: tenofovir-based PrEP for PWOH; antiretroviral therapy (ART) for PWH, MOUD, screening/treatment/referral for STIs and HCV, basic primary care, referrals for housing, food, and social services. Eligibility: reported HIV sexual/drug-related risks for PWOH with OUD; not on, but willing to start MOUD. Primary outcomes at 26 weeks: alive, taking HIV PrEP or ART (verified by blood), and being on MOUD (verified by urine plus evidence of being on MOUD). Generalized Linear Models estimated primary and certain secondary outcomes with arm and site as covariates; Cox proportional hazards modeled death outcomes. Results: Table presents demographics, primary and secondary outcomes by serostatus and study arm. There were no significant differences in primary outcomes at 26 weeks, with low evidence of MOUD use across arms and serostatus. There was no difference in HIV-1 RNA suppression by study arm among PWH; no difference in PrEP use among PWOH at the 26-week visit. HIV seroincidence among PWOH was 0.92 per 100PY. Uptake of peer navigation was high in both arms. A 64% reduction in all-cause mortality was observed for experimental vs. active control arms but, did not reach statistical significance. Conclusions: The strong reduction in all-cause mortality for the integrated services vs. control arm signals the likely value of delivering this care strategy to PWID using a mobile unit. Findings suggest that reaching and engaging PWID in need of comprehensive care “where they are at” may prevent deaths and highlights the potential power of the HPTN 094 mobile unit in addressing multiple health crises simultaneously.

Oral Abstracts

49

CROI 2025