Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.

TitleTemporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.
Publication TypeJournal Article
Year of Publication2017
AuthorsMukerji, SS, Misra, V, Lorenz, D, Cervantes-Arslanian, AM, Lyons, JL, Chalkias, S, Wurcel, A, Burke, D, Venna, N, Morgello, S, Koralnik, IJ, Gabuzda, D
JournalJ Acquir Immune Defic Syndr
Volume75
Issue2
Pagination246-255
Date Published2017 Jun 01
ISSN1944-7884
KeywordsCD4 Lymphocyte Count, Drug Resistance, Viral, External, Female, HIV Infections, HIV-1, Humans, Immune Evasion, Male, Middle Aged, Retrospective Studies, RNA, Viral, United States, Viral Load
Abstract

BACKGROUND: Cerebrospinal fluid (CSF) viral escape is an increasingly recognized clinical event among HIV-1-infected adults. We analyzed longitudinal data and drug-resistance mutations to characterize profiles of HIV-1-infected patients on antiretroviral therapy with discordant CSF and plasma HIV-1 RNA levels.METHODS: Forty-one cases of CSF escape defined as detectable CSF HIV-1 RNA when plasma levels were undetectable, or HIV-1 RNA >0.5-log higher in CSF than plasma were identified from Boston Hospitals and National NeuroAIDS Tissue Consortium (NNTC) from 2005 to 2016.RESULTS: Estimated prevalence of CSF escape in Boston and NNTC cohorts was 6.0% and 6.8%, respectively; median age was 50, duration of HIV-1 infection 17 years, CD4 count 329 cells/mm and CD4 nadir 21 cells/mm. Neurological symptoms were present in 30 cases; 4 had repeat episodes of CSF escape. Cases were classified into subtypes based plasma HIV-1 RNA levels in the preceding 24 months: high-level viremia (1000 copies/mL), low-level viremia (LLV: 51-999 copies/mL), and plasma suppression with CSF blip or escape (CSF RNA <200 or ≥200 copies/mL). High-level viremia cases reported more substance abuse, whereas LLV or plasma suppression cases were more neurosymptomatic (81% vs. 53%); 75% of repeat CSF escape cases were classified LLV. M184V/I mutations were identified in 74% of CSF samples when plasma levels were ≤50 copies per milliliter.CONCLUSIONS: Characteristics frequently observed in CSF escape include HIV-1 infection >15 years, previous LLV, and M184V/I mutations in CSF. Classification based on preceding plasma HIV RNA levels provides a useful conceptual framework to identify causal factors and test therapeutics.

DOI10.1097/QAI.0000000000001362
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID28328546
PubMed Central IDPMC5452976
Grant ListU01 MH083507 / MH / NIMH NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
R01 MH097659 / MH / NIMH NIH HHS / United States
T32 AG000222 / AG / NIA NIH HHS / United States
R01 DA030985 / DA / NIDA NIH HHS / United States
U01 MH083501 / 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
UL1 TR001102 / TR / NCATS NIH HHS / United States