CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

for demographic (e.g., age), socioeconomic, and HIV-related factors. ART utilization prior to ND diagnosis was also explored. Results: There were 796 unique cases (6.1%) of ND identified (157 mild and 732 advanced). Differences in ND cases vs. non-cases were found by age (57 vs. 46, p<0.01), race/ethnicity (non-Hispanic white=15.6% vs 12.7%, p<0.01), insurance status (private=23.1% vs. 30.7%, p<0.01), and viral load (not suppressed <200 copies/mL=17.8% vs. 21.0%; p<0.05). Incidence decreased slightly for mild ND and increased for advanced (p<0.001) over the study period. Pre-ND diagnoses of DM and CVD were highly prevalent for both mild ND (40.3%, 67.5%, respectively) and advanced ND (29.1%, 56.6%). In adjusted logistic regression models, PWH with ND were more likely to have major depressive disorder (MDD), diabetes mellitus, CVD, chronic kidney disease, toxoplasmosis, opportunistic infections, and anxiety (Table). Of those with available ART data prior to ND diagnosis, the greatest prevalence of utilization was INSTI-based (32.9%), Dual class (22.8%), and PI-based (22.1%) ART. Conclusions: While the prevalence of PWH with ND in our analysis was low, the incidence of advanced ND is increasing. PWH with ND were more likely to have several comorbidities, indicating increased burden of disease. Identification of prevalent pre-ND disorders may help elucidate ND development among aging PWH.

(β=-.73, SE =.316, p =.022), such that inflammation was associated with worse psychomotor functioning for older PWH (β=-1.51, SE =.470, p =.001) but not younger PWH ( p >.10). The SII-psychomotor functioning association remained significant in a subgroup of virally suppressed older PWH (N=606; β=-1.15, SE =.525, p =.029). Conclusions: The SII was associated with poorer performance in multiple neurocognitive domains and globally in PWH. Most of these effects were not modified by age, except for psychomotor speed, highlighting domain specific sensitivity to inflammation among older PWH and treatment-related implications (e.g., anti-inflammatory medications). Findings also highlight the utility of the SII in identifying psychomotor functioning in older PWH, that should be further examined for its prognostic value in future studies.

Poster Abstracts

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First-in-Human Study of a Long-Acting Injectable 3 Antiretroviral Drug Combination Nanoparticle Rachel A. Bender Ignacio 1 , Christine Johnsson 1 , Matthew Hartman 1 , Simone Perazzolo 1 , Eli P. Burnham 1 , Phoebe Bryson-Cahn 1 , Claborne Youngblood 1 , Pablo Belaunzarán-Zamudio 2 , Keith Crawford 2 , Edward P. Acosta 3 , Zachary R. Stephen 1 , Brett S. Hanscom 4 , Ann Melvin 5 , Ann C. Collier 1 , Rodney J. Y. Ho 1 , for the Targeted Long-Acting Combination Antiretroviral Therapy (TLC-ART) Program 1 University of Washington, Seattle, WA, USA, 2 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 Fred Hutchinson Cancer Center, Seattle, WA, USA, 5 Seattle Children's Hospital, Seattle, WA, USA Background: Long-Acting antiretroviral therapy (LA-ART) is considered an integral tool to improve adherence and decrease stigma, but its global implementation has met barriers, including cost and resources for administration. The TLC-ART program, a public-private partnership, engineered a novel 3-drug combination nanoparticle (DcNP) for subcutaneous injection containing lopinavir (LPV), ritonavir (RTV), and tenofovir (TVF) “TLC-ART 101” bound with DSPC and mPEG-DSPE lipid excipients. We report safety and pharmacokinetics (PK) from the completed first-in-human (FIH) study, NCT06850728. Methods: This open-label FIH study with pharmacologically guided adaptive design allowed for dose escalation or de-escalation between cohorts. TLC-ART 101 DcNP contains 10.4mg of LPV, 2.7mg RTV, and 6.1mg of TFV per ml. Participants were healthy and without HIV. The LOW Dose cohort received 1.5ml; MID-Dose received 2x 1.5ml each; HIGH Dose received 2x 2ml each as subcutaneous peri-umbilical injection(s) on Day 0 as a single dose. Participants were evaluated over 24hrs and on days 1, 2, 3, 7, 10, 14, 21, 28, 35, 49, 57, and 63. Blood was collected for plasma PK analysis and safety. Results: We enrolled 8 men and 4 women, (mean age 37; 50% non-white). Injection site reactions (ISR) included 7 Grade 1 ISRs and 3 Grade 2 ISRs (erythema). A HIGH Dose participant experienced anaphylaxis 6hrs after dosing, recovering after intervention including epinephrine. The dose was then decreased by 25% and the final 3 participants (MID) experienced no systemic AEs. Additional AEs: Gr 2 Lip swelling (LOW), Gr 2 erythematous rash (HIGH), Gr 1 generalized pruritis (n=2, LOW, HIGH); no gastrointestinal side effects occurred. No participants had increases in IgE or tryptase after dosing. Each drug average C max was within the safety parameters of oral dosing. Average T 1/2 was 33 days for LPV, 1 day for RTV, and 4 days for TFV. Drug components were detectable on average at 63 days (LPV), 4 days (RTV), and 20 days (TFV).

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Systemic Immune-Inflammation Index Links to Slower Psychomotor Speed in Older People With HIV Crystal Wang 1 , Raymond Jones 2 , Evelyn Iriarte 3 , Jun Yeong Byun 2 , Kristen Krause 4 , Casey Xavier Hall 5 , Ronald Ellis 6 , Mariana Cherner 1 , Suzi Hong 1 , David Moore 1 , Scott L. Letendre 1 , Jennifer Iudicello 6 1 University of California San Diego, La Jolla, CA, USA, 2 University of Alabama at Birmingham, Birmingham, AL, USA, 3 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 4 Rutgers New Jersey Medical School, Newark, NJ, USA, 5 Florida State University, Tallahassee, FL, USA, 6 University of California San Diego Medical Center, La Jolla, CA, USA Background: Persistent inflammation and immune activation are hallmark features of HIV disease, and associated with long-term brain health disorders, such as neurocognitive impairment even in treated people with HIV (PWH). As PWH age, the interactions between aging, inflammation, and brain health are important to understand. The Systemic Immune-Inflammation Index (SII) has prognostic value as an indicator of immune activation and systemic inflammation in clinical conditions, but few studies have examined its utility in PWH. The current study examined the hypothesis that inflammation, measured by the SII, would have worse effects on neurocognition for older than younger PWH. Methods: Participants were 1,867 PWH enrolled in studies affiliated with the HIV Neurobehavioral Research Program from 2003-2023. Neurocognition was assessed using demographically adjusted T-scores across 7 domains. The SII was calculated from cell counts ([neutrophils X platelets]/lymphocytes). Multiple linear regressions tested the effects of inflammation, age (dichotomized as older [>50] or younger [<50]), and their interaction on neurocognition, adjusting for covariates (e.g., sex, nadir and current CD4, antiretroviral therapy (ART) use, viral suppression, and estimated duration of HIV). Results: Across all participants (80% male; 46% older; 35% White; 66% AIDS; 61% virally suppressed; 81% on antiretroviral therapy [ART]), the SII was associated with lower global neurocognition, verbal fluency, processing speed, learning, and recall ( p <.05). Although there was no difference in SII by age ( p >.10), there was a significant age x SII interaction for psychomotor speed

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