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.
Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Mukerji, SS, Misra, V, Lorenz, DR, Uno, H, Morgello, S, Franklin, D, Ellis, RJ, Letendre, S, Gabuzda, D |
Journal | Clin Infect Dis |
Volume | 67 |
Issue | 8 |
Pagination | 1182-1190 |
Date Published | 2018 09 28 |
ISSN | 1537-6591 |
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 | 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. |
DOI | 10.1093/cid/ciy267 |
Alternate Journal | Clin Infect Dis |
PubMed ID | 29617912 |
PubMed Central ID | PMC6160603 |
Grant List | U01 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 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 |