PHASE I II EVALUATION OF NEVIRAPINE ALONE AND IN COMBINATION WITH ZIDOVUDINE FOR INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS/

In these Phase I/II open-label clinical trials, 62 persons with human immunodeficiency virus type 1 (HIV-1) infection and CD4(+) cell counts <400/ mm(3) received nevirapine at doses of 12.5, 50, and 200 mg/day, alone or in combination with zidovudine, 200 mg q8h. Nevirapine was w ell tolerated in the doses tested. Mean steady-state trough levels wer e 0.23, 1.1, and 1.9 mu g/ml for the 12.5, 50, and 200 mg/day doses, r espectively. Early suppression of p24 antigen levels and increase in C D4(+) cell count were reversed following rapid emergence of virus less susceptible to nevirapine. Resistant strains were isolated from all p articipants by 8 weeks. Nevertheless, reduction of p24 antigen levels to <50% of baseline values persisted for 12 weeks or more in four of s even persons who received 200 mg nevirapine/day in combination with zi dovudine: these individuals had been antigenemic on long-term zidovudi ne therapy, This study demonstrates a direct relationship between drug resistance and effects on surrogate markers in HIV-1 infection.