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Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure.

Spudich S, Lollo N, Liegler T, Deeks SG, Price RW

Department of Neurology, San Francisco General Hospital, University of California, San Francisco, CA 94110-3518, USA. sspudich@sfgh.ucsf.edu

OBJECTIVE: To characterize the effect of partially suppressive combination antiretroviral therapy on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV)-1 RNA levels and CSF inflammation. DESIGN: The study was a cross-sectional analysis of 139 HIV-1-infected subjects without active neurological disease, categorized as having successful therapy (plasma HIV-1 RNA level < or =500 copies/mL), having failure of therapy (plasma HIV-1 RNA level >500 copies/mL), or not receiving therapy. The control group consisted of 48 HIV-negative subjects. CSF and plasma HIV-1 RNA assays had a lower limit of quantification of 2.5 copies/mL. Genotypic resistance testing was performed on a subset of subjects. RESULTS: Of the 47 subjects with successful therapy, CSF HIV-1 RNA levels were <2.5 copies/mL in 34 (72%). Only 1 had an HIV-1 RNA level >500 copies/mL. Although plasma HIV-1 RNA levels were similar in 35 subjects with failed therapy and 57 of those not receiving therapy (P=.84), CSF HIV-1 RNA levels were at least 10-fold lower in subjects with failed therapy (P<.0001). This disproportionate effect of treatment on CSF HIV-1 RNA levels was found across the range of plasma HIV-1 RNA levels and was not explained by differences in levels of drug resistance in plasma or CSF. Therapy reduced CSF inflammation in both treated groups. CONCLUSIONS: In our cohort, antiretroviral therapy had a greater effect on HIV-1 RNA levels in CSF than in plasma and reduced intrathecal inflammation, even in the presence of drug resistance.

Published 19 November 2006 in J Infect Dis, 194(12): 1686-96.
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