CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1169 Epigenetic Age Acceleration and Mortality Among Persons Who Inject Drugs With Poorly Controlled HIV Jing Sun 1 , David W. Sosnowski 1 , April Shu 2 , Hsing-Yu Hsu 1 , Jill A. Rabinowitz 3 , Shruti H. Mehta 1 , Damani A. Piggott 1 , Brion S. Maher 1 , Gregory Kirk 4 , for the AIDS Linked to the Intravenous Experience (ALIVE) Study Group 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 University of Southern California, Los Angeles, CA, USA, 3 Rutgers University, Piscataway, NJ, USA, 4 The Johns Hopkins University, Baltimore, MD, USA Background: HIV infection and substance use have been associated with accelerated epigenetic aging. However, limited data exist on the long-term implications associated with age acceleration and HIV among persons who inject drugs (PWID). Methods: We included participants from the AIDS Linked to the Intravenous Experience (ALIVE) study, a community-based cohort of PWID. DNA was isolated from buffy coat samples and treated with bisulfite before being analyzed using the Illumina MethylationEPIC BeadChip. Four measures of epigenetic age were generated: PhenoAge, Horvath age, Hannum age, and GrimAge. All participants were linked annually to the National Death Index-Plus to determine time and vital status since 1988. We used linear mixed effect regressions to compare the trajectories of epigenetic age acceleration and Cox regression to determine the hazard of all-cause mortality by epigenetic age and HIV status. All models controlled for demographics, current injection drug use, and current smoking. Results: Of 396 participants (127 people with HIV [PWH]) with 792 person years of follow-up, the median age at baseline was 48.5 years. Of these, the majority were Black (89%) and male (69%). Compared to people without HIV (PWoH), PWH exhibited age acceleration based on multiple epigenetic clocks. This acceleration was further exacerbated by poorly controlled HIV viral load. People with HIV had 2 years (b = 1.79, 95% CI = 0.74, 2.84) and 4 years (b = 4.00, 95% CI = 2.30, 5.69) of age acceleration in GrimAge and PhenoAge, respectively, compared to PWoH. Those with a detectable viral load had faster age acceleration, with 3 years (b = 3.14, 95% CI = 2.13, 4.15) and ~7 years (b = 6.65, 95% CI = 5.01, 8.28) of GrimAge and PhenoAge acceleration, respectively. No differences were observed using Horvath’s clock. Both HIV and epigenetic age acceleration were independently associated with all-cause mortality. Compared to PWoH demonstrating PhenoAge deceleration, PhenoAge acceleration with or without HIV was associated with a 3.28 (95% CI: 2.06, 5.02) and 2.12 (95% CI: 1.32, 3.41) times higher hazard of all-cause mortality, respectively. Conclusions: HIV infection and detectable viral load are associated with epigenetic age acceleration. Age acceleration and HIV infection independently and jointly increase mortality risk among persons who inject drugs. These findings highlight the importance of addressing molecular aging to reduce mortality burden among PWID.

1170 The HIV Epidemic Is Growing Faster in Countries Excluded From Gilead Voluntary Licenses Samuel Cross 1 , Toby Pepperrell 2 , Cassandra Fairhead 3 , Andrew Hill 4 1 NHS Greater Glasgow and Clyde, Glasgow, UK, 2 University of Edinburgh, Edinburgh, UK, 3 Royal Free Hospital, London, UK, 4 University of Liverpool, Liverpool, UK Background: There were 1.3 million new HIV acquisitions worldwide in 2023, far over UNAIDS target of <370,000 by 2025. Novel injectable pre-exposure prophylaxis (PrEP), lenacapavir (LEN), has superior efficacy to oral TDF/FTC. Gilead are drafting a voluntary license (VL) for LEN. We analysed the rate of HIV epidemic growth for countries inside and outside of the existing Gilead VL for tenofovir alafenamide (TAF). This VL excludes middle-income countries (MICs) in North Africa, the Middle East, South America, and Asia. Countries excluded from VLs pay higher prices for drugs, restricting access. LEN is priced at $40,000 per person per year (pppy) in the US, versus predicted costs of production of $40-$100 per person-year. Methods: Epidemiological data were collected from the UNAIDS AIDSinfo 2023 database, which analyses country-level data using the Spectrum model. We extracted epidemic size, HIV acquisitions, change in acquisition rate, incidence in key risk populations including men who have sex with men (MSM) and people who inject drugs (PWID) and MTCT, for countries inside and outside the Gilead VL for TAF. Results were supplemented by PUBMED/EMBASE searches and national reports with most recent estimates for Russia and China (2021). Results: The TAF VL covered 29,615,800 people living with HIV (PLHIV) and 808,900 new HIV acquisitions in 2023. Excluded MICs constitute 4,497,600 PLHIV and 288,189 new HIV acquisitions. Change in new acquisitions from 2010 to 2023 was +55.3% in excluded MICs vs -17.0% included. Excluded high incidence nations include Mexico, Peru, Brazil, Egypt, Bulgaria, Iran, Russia, and China. Annual HIV epidemic growth (incidence: prevalence ratio) was +6.7% for excluded countries vs +4.6% for included countries. High incidence rates are concentrated in key risk populations including MSM (incidence 9.2-16.5% in Mexico, Peru, Brazil, and China) and PWID (3.5-8.1% in Mexico, Bulgaria, Iran, Russia, and China). Average cost of TAF containing products in excluded countries was $7206 pppy versus $189 included. Conclusions: The HIV epidemic is growing faster in countries excluded from the Gilead VL for TAF (+6.7%/year) versus those included (+4.6%/year). Rate of HIV acquisition has risen 55.3% in countries excluded since 2010, while falling 17% for included countries. If the imminent LEN VL includes all LMICs, this would cover 85% of the world’s population, where 95% of new HIV acquisitions are diagnosed, facilitating affordable pricing of LEN as seen in LMICs included in the TAF VL.

Poster Abstracts

1171 Characteristics and Needs of Adult Lifetime Survivors With HIV in the United States, 2015-2022 Margaret A. Lampe 1 , John Weiser 1 , Xin A. Yuan 2 , Sahithi Kalari 1 , Kate Buchacz 1 , Alexis Henderson 2 , Athena Kourtis 1 , Jason Craw 1 , Joseph Prejean 1 , Alexandra Balaji 1 , Linda Beer 1 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 DLH Corporation, Atlanta, GA, USA Background: Advances in HIV care and treatment have substantially extended survival of people with HIV. There is limited knowledge of the current health of the approximately 12,500 persons living with perinatally acquired HIV, i.e., Lifetime Survivors (LS), in the United States. Methods: We used data from the Medical Monitoring Project (MMP), a nationally representative sample of US adults with diagnosed HIV, to examine demographic and clinical characteristics of adult LS. MMP collects annual, cross-sectional data through medical record abstraction (MRA) and interviews. We analyzed data from the 2015-2022 MMP data cycles on persons who reported they were born with HIV or had an HIV diagnosis within 12 months of birth (N=292). We report weighted percentages for key sociodemographic,

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