Pharmacokinetics, Safety, and Activity of Nevirapine in Human Immunodeficiency Virus Type 1-Infected Children

Phase I trials were conducted in human immunodeficiency virus type 1 (HIV-1)-infected children to examine the pharmacokinetics, safety, and antiretroviral activity of nevirapine, a nonnucleoside HIV-1 reverse transcriptase inhibitor. Nevirapine was rapidly absorbed, but the time to peak plasma concentrations increased with higher doses. Clearance was more rapid in chronic dosing studies than predicted by single-dose studies and was more rapid in younger children than in adolescent children. Rash, which occurred in 1 of the 21 study participants, was the single toxicity regarded as nevirapine-related. At doses ≥240 mg/m 2 /day, 5 of 10 children experienced durable suppression of plasma p24 antigen to <50% of baseline values through 8 weeks of nevirapine monotherapy. Viruses resistant to nevirapine were isolated from all children during therapy, but their isolation did not always predict loss of antiviral activity. The evaluation of nevirapine in combination therapy trials is underway in children.