Treatment Benefit on Cerebrospinal Fluid HIV‐1 Levels in the Setting of Systemic Virological Suppression and Failure
Departments of 1Neurology and 2Medicine, San Francisco General Hospital, University of California, San Francisco
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 
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 (
), CSF HIV‐1 RNA levels were at least 10‐fold lower in subjects with failed therapy (
). 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.
Received 11 April 2006; accepted 7 June 2006; electronically published 3 November 2006.
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(See the editorial commentary by McArthur and Letendre, on pages 1628–31.)
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Presented in part: 13th Conference on Retroviruses and Opportunistic Infections, Denver, 5–8 February 2006 (abstract E‐129).
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants R01 NS37660, R01 MH62701, R01 NS43103, K23 MH074466, P30 AI027763, and MO1 RR0008336).