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

J Infect Dis. 1995 Mar;171(3):537-45. doi: 10.1093/infdis/171.3.537.

Abstract

Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at < or = 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 micrograms/mL [15.8 microM]) exceeded the mean IC50 of 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • HIV Core Protein p24 / analysis
  • HIV Infections / drug therapy*
  • Humans
  • Middle Aged
  • Nevirapine
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • RNA, Viral / analysis
  • Reverse Transcriptase Inhibitors*

Substances

  • Antiviral Agents
  • HIV Core Protein p24
  • Pyridines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Nevirapine