High-Dose Nevirapine: Safety, Pharmacokinetics, And Antiviral Effect In Patients With Human Immunodeficiency Virus Infection

• Published in: The Journal of infectious diseases Vol. 171; no. 3; pp. 537 - 545
• Main Authors: Havlir, Diane, Cheeseman, Sarah H., Mclaughlin, Margaret, Murphy, Robert, Erice, Alejo, Spector, Stephen A., Greenough, Thomas C., Sullivan, John L., Hall, David, Myers, Maureen, Lamson, Michael, Richman, Douglas D.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01.03.1995; University of Chicago Press
• Subjects: Adult; AIDS; Antigens; Antiviral Agents - therapeutic use; Antivirals; Dosage; Exanthema; HIV; HIV 1; HIV Core Protein p24 - analysis; HIV Infections - drug therapy; human immunodeficiency virus; Humans; Major Articles; Middle Aged; Nevirapine; Pharmacokinetics; Pyridines - adverse effects; Pyridines - pharmacokinetics; Pyridines - therapeutic use; Reverse Transcriptase Inhibitors; RNA; RNA, Viral - analysis; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/171.3.537

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 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.