Associations between Antiretrovirals and Cognitive Function in Women with HIV

• Type of Material: Article
• Authors: Leah H Rubin, Johns Hopkins University; Yuliang Li, Johns Hopkins University; Kathryn C Fitzgerald, Johns Hopkins University; Raha Dastgheyb, Johns Hopkins University; Amanda aB Spence, Georgetown University; Pauline M Maki, University of Illinois at Chicago; Anjali Sharma, Albert Einstein College of Medicine; Deborah R Gustafson, SUNY Downstate Health Sciences University; Joel Milam, University of Southern California; Kathleen M Weber, Cook County Health and Hektoen Institute of Medicine; Adaora A Adimora, University of North Carolina; Norman J Haughey, Johns Hopkins University; Ighovwerha Ofotokun, Emory University; Margaret A Fischl, University of Miami; Deborah Konkle-Parker, University of Mississippi; Yanxun Xu, Johns Hopkins University; Dionna W Williams, Johns Hopkins University
• Language: English
• Date: 2020-03-24
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511435/bin/NIHMS1579410-supplement-11481_2020_9910_MOESM1_ESM.docx
• Final Published Version (URL): http://dx.doi.org/10.1007/s11481-020-09910-1
• Title of Journal or Parent Work: JOURNAL OF NEUROIMMUNE PHARMACOLOGY
• Volume: 16
• Issue: 1
• Start Page: 195
• End Page: 206
• Keywords: Neurosciences; PHARMACOGENETICS; TREATMENT-NAIVE; HIV; LONG-TERM EXPOSURE; Antiretrovirals; INDIVIDUALS; PHARMACOKINETICS; Science & Technology; OXIDATIVE STRESS; RALTEGRAVIR; Neurosciences & Neurology; Cognition; Life Sciences & Biomedicine; AGE; Heterogeneity; Women; Pharmacology & Pharmacy; NEUROPSYCHOLOGICAL PERFORMANCE; EFAVIRENZ
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology; Health Sciences, Pharmacology

Abstract

Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women’s Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir <250 cells/μL; n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35–55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129). Within each subgroup, we fitted a constrained continuation ratio model via penalized maximum likelihood to examine adjusted associations between recent ART agents and cognition. Most drugs were not associated with cognition. However, among the few drugs, non-nucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitors(PIs) were most commonly associated with cognition, followed by nucleoside reverse transcriptase inhibitors(NRTIs) and integrase inhibitors(IIs). Directionality of ART-cognition associations varied by subgroup. Better psychomotor speed and fluency were associated with ART for women with well-controlled HIV with vascular comorbidities. This pattern contrasts women with profound HIV legacy effects for whom poorer executive function and fluency were associated with ART. Motor function was associated with ART for younger WWH and primarily 35–55 year olds. Memory was associated with ART only for women with poorly-controlled HIV/substance abuse. Findings demonstrate interindividual variability in ART-cognition associations among WWH and highlight the importance of considering sociodemographic, clinical, and behavioral factors as an underlying contributors to cognition. [Figure not available: see fulltext.]