Treatment Benefit on Cerebrospinal Fluid HIV-1 Levels in the Setting of Systemic Virological Suppression and Failure

J Infect Dis. 2006 Dec 15;194(12):1686-96. doi: 10.1086/508750. Epub 2006 Nov 3.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cross-Sectional Studies
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Inflammation / cerebrospinal fluid
  • Male
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid*
  • San Francisco
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Biomarkers
  • RNA, Viral