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

Protease inhibitors were independent predictors of cerebrospinal fluid (CSF) escape in antiretroviral therapy (ART)–experienced human immunodeficiency virus–infected adults. M184V/I combined with thymidine analog mutations were more frequent in adults with CSF escape compared to no escape. These findings suggest optimizing ART may reduce likelihood of CSF escape.
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 (