Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults
Shibani S Mukerji1, Vikas Misra, David Lorenz
1*Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA; †Department of Neurology, Massachusetts General Hospital, Boston, MA; ‡Departments of Neurology and Neurosurgery, Boston Medical Center, Boston, MA; §Department of Neurology, Brigham and Womens Hospital, Boston, MA; ‖Division of NeuroImmunology, Beth Israel Deaconess Medical Center, Boston, MA; ¶Department of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA; #Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY; and **Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.
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.
