Date Published:
2018 09 28

Publication Type:
Journal Article

Authors:

S.S. Mukerji
V. Misra
D.R. Lorenz
H. Uno
S. Morgello
D. Franklin
R.J. Ellis
S. Letendre
D. Gabuzda

Secondary:
Clin Infect Dis

Volume:
67

Pagination:
1182-1190

Issue:
8

PMID:
29617912

URL:
https://pubmed.ncbi.nlm.nih.gov/29617912

DOI:
10.1093/cid/ciy267

Keywords:
Adult;Aged;Anti-HIV Agents;CD4 Lymphocyte Count;Drug Resistance, Viral;Female;Genotype;HIV;HIV Infections;HIV-1;Humans;Male;Middle Aged;Prospective Studies;RNA, Viral;United States;Viral Load;Young Adult

Abstract:
<p>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.</p>