SAFETY AND ANTIVIRAL ACTIVITY OF COMBINATION THERAPY WITH ZIDOVUDINE,ZALCITABINE, AND 2 DOSES OF INTERFERON-ALPHA(2A) IN PATIENTS WITH HIV- AIDS CLINICAL-TRIALS GROUP-STUDY-197

We conducted a three-arm, randomized, phase II study to evaluate the c ombination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) al one or with one of two interferon-alpha(2a) doses (1 mIU or 6 mIU dail y). Primary study endpoints included toxicity and changes from baselin e for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at we eks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cel ls/mm(3) were enrolled; four patients discontinued therapy within 2 we eks. 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 hem atologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Pla sma HIV-1 RNA reductions were noted across all treatment groups at wee k 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combi nation groups at week 24 (p < 0.001). Mean reductions in HIV-1 RNA at week 8 were 0.94, 1.29, and 1.40 log(10), respectively, for the nucleo side, 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-alpha(2a) to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.