Phase I study of atevirdine, a nonnucleoside reverse transcriptase inhibitor, in combination with zidovudine for human immunodeficiency virus type 1 infection. ACTG 199 Study Team.
Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.
Reichman
R C
RC
Department of Medicine, University of Rochester School of Medicine & Dentistry, NY 14642.
Morse
G D
GD
Demeter
L M
LM
Resnick
L
L
Bassiakos
Y
Y
Fischl
M
M
Para
M
M
Powderly
W
W
Leedom
J
J
Greisberger
C
C
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors; D012449:Safety; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D010879:Piperazines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; C076632:atevirdine