Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r² = 0.378, P = .019), minimum plasma concentration (C(min); r² = 0.359, P = .023), maximum plasma concentration (C(max); r² = 0.340, P = .028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir C(min) (47.5%) and AUC (27.4%) and, to a lesser extent, C(max) (11%). Plasma HIV RNA values were < 1/2 0 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.