CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

suggest complex associations between ART regimens and cognition, such that specific ART combinations rather than individual agents are associated with cognition. Future studies should consider complete drug regimens when assessing the risk of long-term neuropsychiatric complications of ART, with attention to the highlighted drug combinations. The figure, table, or graphic for this abstract has been removed. Phenotyping Risk of Polypharmacy and Cognitive Impairment in ACTG A5322: "HAILO" Robert Paul 1 , Kristine M. Erlandson 2 , Kunling Wu 3 , Scott L. Letendre 4 , Jacob Bolzenius 1 , Katherine Tassiopoulos 3 , Kyu Cho 1 , Qing Ma 5 , Ronald J. Ellis 6 , Priya Kosana 7 , Julie Mannarino 1 , Shelli Farhadian 7 , for the ACTG A5322 Study Team 1 University of Missouri St Louis, St Louis, MO, USA, 2 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 University of California San Diego, La Jolla, CA, USA, 5 University at Buffalo, Buffalo, NY, USA, 6 University of California San Diego, San Diego, CA, USA, 7 Yale University, New Haven, CT, USA Background: Polypharmacy is associated with worse cognitive health among people with HIV (PWH), however explanatory models have not been established. This study leveraged data from a large and well characterized cohort of virally suppressed individuals age 40 and older to identify risk factors that explain the association between polypharmacy and cognitive impairment among PWH. Methods: Data obtained at enrollment into ACTG A5322 ("HAILO") were included. Cognitive performance was measured using four tests of verbal learning, attention/psychomotor speed, and fine motor speed and dexterity. Hierarchical density-based spatial clustering, an unsupervised machine learning based algorithm, was used to identify sub-groups based on cognitive performance. Polypharmacy (≥5 non-ART medications), and hyperpolypharmacy (≥10 medications) as well as demographic, clinical, and psychosocial variables were compared across clusters using multinomial regression, adjusted for multiple comparisons. Results: Participants were 870 PWH (18.4% female, 52.2% non-White), with a median age of 51. Analyses identified 8 cognitive clusters. There were no differences in average age across clusters. Cluster 1 (33% of the sample) included participants with the best test scores whereas clusters 6, 7, and 8 (collectively 48%) had the worst test scores. Polypharmacy was more common in clusters 6 and 8 compared to cluster 1 (reference group) and hyperpolypharmacy was more common in clusters 7 and 8 compared to cluster 1 (ps<.05; Table). Participants in clusters 6, 7, and 8 were also more likely to be women, Black or Hispanic, less educated, and have higher rates of cardiovascular disease, diabetes, hepatitis C, peripheral neuropathy, and substance use compared to participants in cluster 1 (ps<.05). Participants in clusters 6, 7, and 8 also reported a shorter duration of ART, lower CD4+ T-cell count and nadir, and lower CD4/CD8 ratio compared to cluster 1. Use of psychoactive medications did not differ between the clusters. Black or Hispanic women were more likely to have polypharmacy or hyperpolypharmacy (OR=1.4; 95th CI [.97-2.0]) and cognitive impairment (OR=2.8; 95th CI [1.7-4.6]) compared to any other demographic group. Conclusion: Psychosocial determinants of health, particularly those that disproportionately impact Black and Hispanic females with HIV, associate with an increased risk for polypharmacy/hyperpolypharmacy and cognitive impairment. Intervention/prevention efforts aimed at these high risk groups are warranted.

PWH at baseline (30.1 vs. 11.7%, p<.001), but not different to PWoH at follow up (8.28 vs. 7.50%, p=1). Mixed effects models showed PWH improved 1.40 points more than PWoH (CI 0.21-2.58, p=.021). Overall sleep quality improved following switch (OR 0.37, p=.001), driven mainly by indicators of disturbed sleep. Rates of depressive symptoms (CESD ≥16) worsened (OR 6.53, p=.016), although baseline differences between PWH and PWoH were present (9.55% vs. 22.11%, p=.004). 104/113 (92.0%) plasma and 93/94 (98.9%) CSF samples were supressed <50 copies/ml at baseline, and 103/122 (84.4%) and 73/77 (94.8%) at follow up. There was 1 case (1.1%) of CSF HIV RNA escape (CSF HIV RNA > plasma) at baseline and 3 (3.9%) at follow up; 3/4 were at low levels (CSF HIV RNA <200 copies/ml) and 1/4 resolved on repeat sampling without change in ART. Conclusion: Rates of low cognitive performance were lower than previously reported in this setting, and no different to PWoH once switched to DTG. Observed improvements in cognitive performance and sleep were likely related to switching away from EFV. The increase in depressive symptoms on DTG is inconclusive due to baseline differences, but warrants further investigation. CSF escape was uncommon on both EFV and DTG.

555

Poster Abstracts

554

Antiretroviral Regimens Are Associated With Cognitive Function in People With HIV Luis Parra-Rodriguez 1 , Jane A. O'Halloran 1 , Yuezhe Wang 2 , Wei Jin 2 , Lang Lang 2 , Raha M. Dastgheyb 3 , Donald Franklin 4 , Ronald J. Ellis 4 , Scott L. Letendre 5 , Qing Ma 6 , Yanxun Xu 2 , Leah H. Rubin 2 1 Washington University in St Louis, St Louis, MO, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 University of California San Diego, San Diego, CA, USA, 5 University of California San Diego, La Jolla, CA, USA, 6 University at Buffalo, Buffalo, NY, USA Background: While modern antiretroviral therapy (ART) is highly effective and safe overall, ART medications can cause neuropsychiatric adverse effects (e.g., poorer cognition). Observational studies addressing cognition have mainly focused on individual ART drugs rather than ART regimens, partly due to statistical limitations. We developed a novel statistical approach to examine the relationship between common ART regimens and cognition in people with HIV (PWH). Methods: We leveraged longitudinal data collected between 2014-2020 from PWH enrolled in CHARTER, NNTC, or NeuroHIV cohorts at UCSD with available ART regimen data concurrent with comprehensive neuropsychological (NP) testing. Novel Bayesian machine learning methods building upon a subset tree kernel approach were developed to estimate the combined effects of ART regimens on NP performance after controlling for relevant covariates. Results: Among 1,702 individuals who participated in 1,928 (mean 1.13) visits, the mean age was 55 (interquartile range [IQR] 49-63) years; 26% were female, 23% were black; 23% were Hispanic; and 72% had HIV RNA <50 copies/mL at study entry. The most common ART regimens used were: 1) dolutegravir (DTG)+abacavir (ABC)+lamivudine (3TC) at 22%, 2) elvitegravir (EVG)+cobicistat (COBI)+tenofovir alafenamide (TAF)+emtricitabine (FTC) at 14%; and 3) efavirenz (EFV)+tenofovir disoproxil fumarate (TDF)+ FTC at 10%. Darunavir (DRV)+COBI+TAF+FTC was associated with worse executive function, learning and memory, while no association was observed with other protease inhibitors. Rilpivirine (RPV)+TAF+FTC and EFV+TDF+FTC were also associated with poorer executive function and memory without effects on learning. DTG+TDF+FTC, DTG+ABC+3TC, and EVG+COBI+TDF+FTC were associated with better learning, memory, and motor function, respectively. Conclusion: Specific ART regimens are associated with worse domain-specific cognitive function. Tenofovir (including TAF or TDF) and FTC were common in such regimens in combination with either DRV+COBI, RPV, or EFV. Our findings

556

Pharmacogenetics of Early Neuropsychiatric Adverse Events After Switching to DTG in Second-Line ART Ying Zhao , Gary Maartens, Rulan Griesel, Graeme A. Meintjes, Phumla Sinxadi University of Cape Town, Cape Town, South Africa Background: Dolutegravir is associated with neuropsychiatric adverse events (NPAEs). We characterised associations between genetic polymorphisms

CROI 2024 150