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CD4 response is correlated with peak plasma concentrations of indinavir in adults with undetectable human immunodeficiency virus ribonucleic acid
Author(s) -
Anderson Peter L.,
Brundage Richard C.,
Kakuda Thomas N.,
Fletcher Courtney V.
Publication year - 2002
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2002.121910
Subject(s) - indinavir , zidovudine , liter , lamivudine , medicine , pharmacokinetics , pharmacodynamics , immunology , gastroenterology , immunopathology , lentivirus , viral disease , sida , pharmacology , human immunodeficiency virus (hiv) , virology , virus , hepatitis b virus
We retrospectively evaluated correlates of increases in CD4 cell count in antiretroviral agent‐naive subjects with fewer than 50 copies per milliliter of plasma human immunodeficiency virus ribonucleic acid who were participating in a study of indinavir, lamivudine, and zidovudine therapy. Pharmacologic data from intensive pharmacokinetic studies and baseline patient characteristics were evaluated as predictors of the increase in CD4 count from baseline to weeks 24, 56, and 80. Relations were investigated with regression analysis. Of all covariates, maximum plasma concentration (C max ) of indinavir was significantly and uniquely associated with increases in CD4 count from baseline to all end points ( P = .002 at week 80; n = 20). At week 80, subjects with a C max greater than the overall group median value of 7 μg/ml had an increase in CD4 count of 358 cells/μl versus 197 cells/μl for those with a C max less than 7 μg/ml ( P = .006). These data suggest distinct pharmacodynamic relations exist for immune reconstitution and suppression of plasma human immunodeficiency virus ribonucleic acid. We hypothesize this new finding may be associated with expression of P‐glycoprotein. Clinical Pharmacology & Therapeutics (2002) 71 , 280–285; doi: 10.1067/mcp.2002.121910