Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma

D. W. Haas, L. A. Clough, B. W. Johnson, V. L. Harris, P. Spearman, G. R. Wilkinson, C. V. Fletcher, S. Fiscus, S. Raffanti, R. Donlon, J. McKinsey, J. Nicotera, D. Schmidt, R. E. Shoup, R. E. Kates, Jr M. Lloyd, B. Larder

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Defining the source of HIV-1 RNA in cerebrospinal fluid (CSF) will facilitate studies of treatment efficacy in the brain. Four antiretroviral drug-naive adults underwent two 48-hr ultraintensive CSF sampling procedures, once at baseline and again beginning on day 4 after initiating three-drug therapy with stavudine, lamivudine, and nelfinavir. At baseline, constant CSF HIV-1 RNA concentrations were maintained by daily entry of at least 104 to 106 HIV-1 RNA copies into CSF. Change from baseline to day 5 ranged from -0.38 to -1.18 Ioglo HIV-1 RNA copies/ml in CSF, and from -0.80 to -1.33 log10 HIV-1 RNA copies/ml in plasma, with no correlation between CSF and plasma changes. There was no evidence of genotypic or phenotypic viral resistance in either CSF or plasma. With regard to pharmacokinetics, mean CSF-to-plasma area-under-the-curve (AUC) ratios were 38.9% for stavudine and 15.3% for lamivudine. Nelfinavir and its active M8 metabolite could not be accurately quantified in CSF, although plasma M8 peak level and AUC0-8 hr correlated with CSF HIV-1 RNA decline. This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma.

Original languageEnglish (US)
Pages (from-to)1491-1502
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume16
Issue number15
DOIs
StatePublished - Oct 10 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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