PHASE-I STUDY OF ATEVIRDINE, A NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR, IN COMBINATION WITH ZIDOVUDINE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

Twenty patients were enrolled in a phase I clinical trial of atevirdin e, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in c ombination with zidovudine for treatment of human immunodeficiency vir us type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals w ere tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these develope d concomitant fever and hepatitis. No hematopoietic, neurologic, or pa ncreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of pati ents treated with atevirdine plus zidovudine had increased CD4 lymphoc yte counts, and HIV isolates from 62% of patients remained sensitive t o atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the ro le of atevirdine in the therapy for HIV infection.