High-dose nevirapine: Safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection

Diane Havlir*, Sarah H. Cheeseman, Margaret Mc Laughlin, Robert Murphy, Alejo Erice, Stephen A. Spector, Thomas C. Greenough, John L. Sullivan, David Hall, Maureen Myers, Michael Lamson, Douglas D. Richman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

Abstract

Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at ≤200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 µg/mL [l5.8µg/M]) exceeded the mean IC50of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.

Original languageEnglish (US)
Pages (from-to)537-545
Number of pages9
JournalJournal of Infectious Diseases
Volume171
Issue number3
DOIs
StatePublished - Mar 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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