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

Abstract

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.