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.

TitleImpact 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.
Publication TypeJournal Article
Year of Publication2018
AuthorsMukerji, SS, Misra, V, Lorenz, DR, Uno, H, Morgello, S, Franklin, D, Ellis, RJ, Letendre, S, Gabuzda, D
JournalClin Infect Dis
Volume67
Issue8
Pagination1182-1190
Date Published09/2018
ISSN1537-6591
KeywordsInternal
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.

DOI10.1093/cid/ciy267
Alternate JournalClin. Infect. Dis.
PubMed ID29617912
PubMed Central IDPMC6160603
Grant ListU01 MH083507 / MH / NIMH NIH HHS / United States
R24 MH059724 / MH / NIMH NIH HHS / United States
K24 MH097673 / MH / NIMH NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
R01 MH097659 / MH / NIMH NIH HHS / United States
T32 AG000222 / AG / NIA NIH HHS / United States
R24 NS045491 / NS / NINDS NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
K23 MH115812 / MH / NIMH NIH HHS / United States
R24 MH059745 / MH / NIMH NIH HHS / United States
R24 NS038841 / NS / NINDS NIH HHS / United States
N01 MH022005 / MH / WHI NIH HHS / United States
U01 AI069911 / AI / NIAID NIH HHS / United States
U01 MH083501 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
U01 MH083545 / MH / NIMH NIH HHS / United States
U01 MH083506 / MH / NIMH NIH HHS / United States
R01 MH110259 / MH / NIMH NIH HHS / United States
R01 DA040391 / DA / NIDA NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
N01 MH032002 / MH / WHI NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States