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

Shibani S. Mukerji, Vikas Misra, David Lorenz, Anna M. Cervantes-Arslanian, Jennifer Lyons, Spyridon Chalkias, Alysse Wurcel, Deirdre Burke, Nagagopal Venna, Susan Morgello, Igor J. Koralnik, Dana Gabuzda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 3 and CD4 nadir 21 cells/mm 3. 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.

Original languageEnglish (US)
Pages (from-to)246-255
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume75
Issue number2
DOIs
StatePublished - Jun 1 2017

Keywords

  • CSF viral escape
  • HIV-1
  • antiretroviral therapy
  • cerebrospinal fluid
  • drug resistance mutations

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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