CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

598

No Decline in CSF or Plasma Neurofilament Light Chain Levels Post-Early ART Initiation Nametso Kelentse 1 , Yunshan Xu 1 , Yanhong Deng 1 , Jennifer Chiarella 1 , Allison Grubman 1 , Sebastian Romero 1 , Shelli Farhadian 1 , Richard W. Price 2 , Serena Spudich 1 1 Yale University, New Haven, CT, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: Signs of CNS injury in PWH can be detected as early as primary HIV infection (PHI = lab-confirmed HIV acquisition <12 months) prior to ART. It is unknown whether neuronal injury is ongoing during early untreated HIV, and/ or declines post-ART. In a longitudinal CNS study of participants enrolled in PHI, we modeled longitudinal trajectories of CSF and plasma neurofilament light chain (NfL), a sensitive biomarker of active neuronal damage, and examined associations with lab and neuropsychological (NP) parameters in early infection. Methods: NfL concentrations were measured using single molecule array (SIMOA) assay in longitudinal CSF and plasma samples from the observational PISCES PHI study (2004-2014, San Francisco), in which some participants chose to delay ART. Linear-mixed models were employed to determine CSF and plasma NfL trajectories pre- and post-ART, adjusting for longitudinal HIV RNA levels and baseline age. Associations were assessed in pre- and post-ART longitudinal NfL levels between CSF and blood, and parameters including age, CSF viral load (VL), and NPZ-11, a total summed z-score from an 11 test NP battery done at each visit. Results: At baseline PHI participants (n=42, 100% male) were median 39 years of age (IQR:31-46) and had estimated duration of infection 126 (75-184) days; 97.6% were ART-naïve. The 166 CSF and 208 plasma samples assayed reflected data from >2 (range:1-8) visits pre- and post-ART with >6 months follow-up intervals. 98% of participants had suppressed plasma VL post-ART. Overall CSF NfL increased with age (p=0.003) while plasma NfL increased with both age and plasma VL (p=0.004 and p=0.019). Plasma NfL strongly correlated with CSF NfL (p=0.002). CSF NfL tended to increase pre-ART, but this was not statistically significant (slope=0.02, p=0.44). There was no significant change in CSF NfL post-ART, nor difference between these pre- and post-ART slopes (see Figure). No significant changes in NfL levels were observed in plasma. CSF and plasma NfL levels did not associate with NPZ-11 scores pre-ART, while plasma NfL associated with a 5.1 decrease in NPZ-11 score (p<0.001) post-ART. Conclusions: In this longitudinal data from a PHI cohort, CSF NfL did not decline over time either pre- or post- ART. These findings suggest the presence of ongoing neuronal injury throughout early infection. Further studies with longer follow-up are needed to understand the clinical significance of neuronal injury observed in PWH in early infection. The figure, table, or graphic for this abstract has been removed. Polypharmacy Is Associated With Neuronal Injury in PWH Priya Kosana 1 , Allison Grubman 2 , Kunling Wu 3 , Katherine Tassiopoulos 3 , Qing Ma 4 , Scott L. Letendre 5 , Kristine M. Erlandson 6 , Shelli Farhadian 2 , for the ACTG A5322 (HAILO) Study Team 1 East Carolina University, Greenville, NC, USA, 2 Yale University, New Haven, CT, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 University at Buffalo, Buffalo, NY, USA, 5 University of California San Diego, La Jolla, CA, USA, 6 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: Polypharmacy, or the use of five or more non-ART prescription medications, promote neurologic disorders and geriatric syndromes. However, it is unknown if this is mediated by neuronal damage incurred by multiple medications, by inflammation, or by high comorbidity burden necessitating the use of multiple medications. To better understand how polypharmacy influences neurologic disorder in people with HIV (PWH) we compared polypharmacy, biomarkers of neuronal injury and inflammation, and gait speed and recurrent falls. Methods: Data and specimens from 600 PWH of the longitudinal AIDS Clinical Trials Group (ACTG) A5322 (HAILO) study were included. Inclusion criteria were plasma HIV RNA below 200 cps/mL at study entry. Neurofilament light chain (NfL) levels were quantified using a single-molecule array assay in duplicate. Neopterin was quantified by ELISA and soluble CD14 (sCD14) was assessed using a bead-based assay (Eve Tech). Multivariable logistic regression analysis was utilized to assess the relationship between polypharmacy and NfL, sCD14, and neopterin (biomarkers of monocyte/microglial cell activation). All biomarkers were analyzed as continuous variables.

Results: Six hundred HAILO participants were included, with median age of 54 years (range 40 to 78); 81% were male sex, 33% were Black Non-Hispanic race, 20% were Hispanic, and 39% with polypharmacy. Higher NfL was associated with male sex (OR 1.18 [1.06, 1.31]), older age (OR 1.52 [1.16, 2.01]), and comorbidity burden (OR for 2 comorbidities: 1.3 [1.13, 1.48]; OR for 3 comorbidities: 1.96 [1.61, 2.39]; OR for 4 comorbidities: 3.23 [2.17, 4.80]). Analyzed comorbidities are CVD, T2 diabetes mellitus, liver disease, kidney disease, and peripheral neuropathy. In multivariable analysis, after adjusting for age, sex, and comorbidity burden, polypharmacy had a modest but significant association with elevated plasma NfL (OR 1.16 [ 1.07, 1.26]), but not with sCD14 or neopterin. Elevated plasma NfL (OR 1.24 [1.05, 1.46]) and plasma sCD14 (OR 1.11 [1.01, 1.22] were associated with recurrent falls (more than one fall in 6 months), but not with slow gait speed. Conclusions: In older PWH, both polypharmacy and recurrent falls associate with elevated levels of NfL after accounting for comorbidities that could influence the outcomes. These results support other data that polypharmacy contributes to neurologic disorders in older PWH. Medication management may improve brain health and geriatric syndromes in PWH.

Poster Abstracts

600

Plasma CNS Tissue Markers in Heavily Treatment-Experienced PWH in the PRESTIGIO Registry Andrea Calcagno 1 , Martina Strano 2 , Riccardo Lolatto 3 , Riccardo Vercesi 2 , Alessandra Mandelli 4 , Miriam Antonucci 5 , Vincenzo Spagnuolo 3 , Tommaso Clemente 3 , Daniela Francisci 6 , Giovanni Cenderello 7 , Ornella Schiopppa 8 , Laura Comi 9 , Roberto Furlan 4 , Antonella Castagna 3 , Paola Cinque 2 , for the PRESTIGIO Study Group 1 University of Turin, Turin, Italy, 2 Ospedale San Raffaele, Milano, Italy, 3 IRCCS San Raffaele Scientific Institute, Milan, Italy, 4 IRCCS Ospedale San Raffaele, Milan, Italy, 5 Amedeo di Savoia Hospital, Torino, Italy, 6 University of Perugia, Perugia, Italy, 7 Sanremo Hospital, Sanremo, Italy, 8 CRO Aviano National Cancer Institute, Aviano, Italy, 9 ASST Papa Giovanni XXIII, Bergamo, Italy Background: Heavily treatment-experienced (HTE) persons with HIV (PWH) are characterized by long infection and treatment history, resistant viruses, and a significant burden of concomitant diseases. Since these features may be associated with HIV replication in the Central Nervous System (CNS), this study aimed to assess plasma CNS tissue markers in HTE versus controls. Methods: HTE cases were selected from the PRESTIGIO registry (Italian multicenter cohort enrolling PWH with documented four-class drug resistance) and stratified according to HIV RNA below (VS) or above 50 c/mL (VF) in their first sample in 2021-2023. Controls were consecutively treated > 50-year-old PWH with VS. PWH with ongoing CNS disorders were excluded. Plasma samples were analyzed by SIngle MOlecule Array (SIMOA SR-X, Quanterix Corp., Boston, MA, USA) for neuronal damage markers (neurofilament-light chain, NFL and total Tau protein), astrocyte activation (Glial Fibrillary Acidic Protein, GFAP) and ubiquitin-proteasome involvement (Ubiquitin C-terminal Hydrolase, UCH-L1). Results: We included 84 controls, 106 HTE/VS and 32 HTE/VF (Table). NFL, tau and GFAP levels were significantly lower in HTE than in controls, with significant correlations between the four markers (all p<.001). Higher age correlated to higher NFL (p<.001), GFAP (p<.001) and UCH-L1 (p=.040); male sex with lower GFAP (p=.018) and tau (p<.001); and HIV acquired at birth with lower GFAP (p=.012). In HTE, lower tau was associated with fostemsavir (p=.049) and doravirine use (p=.037) and lower GFAP with darunavir (p=.009). In HTE/ VF plasma HIV RNA inversely correlated to NFL (p=.048). Multivariate linear regression, corrected for age, sex, study group, body mass index (BMI) and significant variables at bivariate analyses, was performed to identify predictors of high levels of each marker. BMI (p=.040, 95%CI 0.045-1.814) and GFAP (p<.001; 95%CI 0.057-0.181) were independent predictors of NFL; CD4 nadir (p=.002; 95%CI 0.001-0.003), current CD4 (p=.009; 95%CI -0.002-0.000) and male sex (p=0.003; -1.199-0.255) of tau; age (p<.001; 95%CI 3.634-6.015), BMI

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CROI 2025 161