High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection.
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.
Havlir
D
D
Department of Medicine, University of California, San Diego.
Cheeseman
S H
SH
McLaughlin
M
M
Murphy
R
R
Erice
A
A
Spector
S A
SA
Greenough
T C
TC
Sullivan
J L
JL
Hall
D
D
Myers
M
M
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D019829:Nevirapine; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine