TY - JOUR
T1 - Temporal Patterns and Drug Resistance in CSF Viral Escape among ART-Experienced HIV-1 Infected Adults
AU - Mukerji, Shibani S.
AU - Misra, Vikas
AU - Lorenz, David
AU - Cervantes-Arslanian, Anna M.
AU - Lyons, Jennifer
AU - Chalkias, Spyridon
AU - Wurcel, Alysse
AU - Burke, Deirdre
AU - Venna, Nagagopal
AU - Morgello, Susan
AU - Koralnik, Igor J.
AU - Gabuzda, Dana
N1 - Funding Information:
Supported by NIH grants to D.G. (RO1 MH097659, RO1 MH110259, R01 DA030985). Training and educational support for S.S.M was provided by NIH T32-AG000222. Additional support for S.S.M included Harvard Catalyst Master's Program in Clinical and Translational Investigation funded by the NIH Clinical and Translational Science Award Program (1UL1-TR001102), and Catalyst Biostatistical Consultation with contributions from Harvard Medical School and affiliated hospitals. Financial support for the NNTC was provided through the following cooperative agreements from the National Institutes of Health U01MH083507; U01MH083501; U01MH083500; U01MH083506; U01MH083545.
Publisher Copyright:
© 2017 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - CSF viral escape
KW - HIV-1
KW - antiretroviral therapy
KW - cerebrospinal fluid
KW - drug resistance mutations
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U2 - 10.1097/QAI.0000000000001362
DO - 10.1097/QAI.0000000000001362
M3 - Article
C2 - 28328546
AN - SCOPUS:85015888418
VL - 75
SP - 246
EP - 255
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 2
ER -