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/mm3 received nevirapine at doses of 12.5, 50, and 200 mg/day, alone or in combination with zidovudine, 200 mg q8h. Nevirapine was well tolerated in the doses tested. Mean steady-state trough levels were 0.23, 1.1, and 1.9 micrograms/ml for the 12.5, 50, and 200 mg/day doses, respectively. Early suppression of p24 antigen levels and increase in CD4+ cell count were reversed following rapid emergence of virus less susceptible to nevirapine. Resistant strains were isolated from all participants by 8 weeks. Nevertheless, reduction of p24 antigen levels to < 50% of baseline values persisted for 12 weeks or more in four of seven persons who received 200 mg nevirapine/day in combination with zidovudine: these individuals had been antigenemic on long-term zidovudine therapy. This study demonstrates a direct relationship between drug resistance and effects on surrogate markers in HIV-1 infection.
Cheeseman
S H
SH
University of Massachusetts Medical School, Worcester.
Havlir
D
D
McLaughlin
M M
MM
Greenough
T C
TC
Sullivan
J L
JL
Hall
D
D
Hattox
S E
SE
Spector
S A
SA
Stein
D S
DS
Myers
M
M
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors; D014481:United States; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine