Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-alpha2a in patients with HIV. AIDS Clinical Trials Group Study 197.
We conducted a three-arm, randomized, phase II study to evaluate the combination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) alone or with one of two interferon-alpha2a doses (1 mIU or 6 mIU daily). Primary study endpoints included toxicity and changes from baseline for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at weeks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cells/mm3 were enrolled; four patients discontinued therapy within 2 weeks. Adverse event rates were 37%, 32%, and 60%, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups. Increasing doses of interferon resulted in significantly greater hematologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Plasma HIV-1 RNA reductions were noted across all treatment groups at week 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combination groups at week 24 (p < 0.001). Mean reductions in HIV-1 RNA at week 8 were 0.94, 1.29, and 1.40 log10, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups (p = 0.05); no differences were noted at week 24. No differences in CD4 cell counts were seen. The addition of interferon-alpha2a to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.
Fischl
M A
MA
Department of Medicine, University of Miami School of Medicine, Florida 33101, USA.
Richman
D D
DD
Saag
M
M
Meng
T C
TC
Squires
K E
KE
Holden-Wiltse
J
J
Meehan
P M
PM
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000009:adverse effects / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015215:Zidovudine; D016047:Zalcitabine