Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1–Infected Adults in the United States
Year: 2018
Type: article
Study design: Observational Study
Abstract: Background: Cerebrospinal fluid (CSF) viral escape occurs in 4%-20% of human immunodeficiency virus (HIV)-infected adults, yet the impact of antiretroviral therapy (ART) on CSF escape is unclear. Methods: A prospective study of 1063 participants with baseline plasma viral load (VL) ≤400 copies/mL between 2005 and 2016. The odds ratio (OR) for ART regimens (protease inhibitor with nucleoside reverse transcriptase inhibitor [PI + NRTI] vs other ART) and CSF escape was estimated using mixed-effects models. Results: Baseline mean age was 46 years, median plasma VL, and CD4 count were 50 copies/mL, and 424 cells/μL, respectively. During median follow-up of 4.4 years, CSF escape occurred in 77 participants (7.2%). PI + NRTI use was an independent predictor of CSF escape (OR, 3.1; 95% confidence interval, 1.8-5.0) in adjusted analyses and models restricted to plasma VL ≤50 copies/mL (P < .001). Regimens that contained atazanavir (ATV) were a stronger predictor of CSF viral escape than non-ATV PI + NRTI regimens. Plasma and CSF M184V/I combined with thymidine-analog mutations were more frequent in CSF escape vs no escape (23% vs 2.3%). Genotypic susceptibility score-adjusted central nervous system (CNS) penetration-effectiveness (CPE) values were calculated for CSF escape with M184V/I mutations (n = 34). Adjusted CPE values were low (<5) for CSF in 27 (79%), indicating suboptimal CNS drug availability. Conclusions: PI + NRTI regimens are independent predictors of CSF escape in HIV-infected adults. Reduced CNS ART bioavailability may predispose to CSF escape in patients with M184V/I mutations.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciy267
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: U.S. Department of Veterans Affairs, Harvard University, Harvard University Center for AIDS Research, National Institutes of Health, Center for AIDS Research, University of Washington, Veterans Affairs San Diego Healthcare System, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, HIV Neurobehavioral Research Center, University of California, San Diego
Awards: G1205301529, California NeuroAIDS Tissue Network (CNTN), G1469043609, G1481340026, G1551097431, G1573662850, G1575283533, G1597973519, G1622375532, National NeuroAIDS Tissue Consortium Statistics and Data Coordinating Center, G1858258047, G2243934053, G2452681398, G25173860, G255310873, G295270083, G298662785, CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER), California NeuroAIDS Tissue Network, G3350118538, G3377819574, G345173699, G3471390838, National Neurological AIDS Bank, G35826679, G3586383482, G3714781482, G4140207963, G4187187018, The Manahattan HIV Brain Bank, The Manhattan HIV Brain Bank, G4563941654, G4913483794, G5228342661, G5295743212, G5640808573, G600206744, G6184231808, G6942509834, G7029056130, G7512296340, G763453686, NIMH HIV Brain Bank - National Coor. Office (NCO), G8034205434, Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research, G8162860740, G8486655539, G8534000477, G8666639600, G8878913872, HIV Neurobehavioral Research Center, G90079629, G900990252
OpenAlex ID: W2796205149