ZALCITABINE COMPARED WITH ZIDOVUDINE IN PATIENTS WITH ADVANCED HIV-1 INFECTION WHO RECEIVED PREVIOUS ZIDOVUDINE THERAPY

Objective: To evaluate the safety and efficacy of zalcitabine (also kn own as dideoxycytidine [ddC]) in patients with advanced human immunode ficiency virus (HIV) infection. Design: Open-label, randomized study. Setting: AIDS Clinical Trials Units, university-affiliated medical cen ters, and private practice groups. Patients: Patients with the acquire d immunodeficiency syndrome (AIDS) or advanced AIDS-related complex wh o had tolerated zidovudine for 48 weeks or more. Intervention: Fifty-n ine patients received zidovudine (500 to 1200 mg/d) and 52 patients re ceived zalcitabine (2.25 mg/d). Measurements: The primary end points w ere survival and time to an AIDS-defining event or death. Results: Bec ause significantly more patients withdrew from zidovudine therapy, the median duration of treatment was greater in the zalcitabine group tha n in the zidovudine group (279.0 days compared with 174.5 days; P = 0. 001). The estimated 12-month, event-free probabilities were 53% for th e zalcitabine group and 57% for the zidovudine group (relative risk, 1 .02; 95% CI, 0.5 to 2.2). The estimated 12-month survival rates were 8 1% for the zalcitabine group and 75% for the zidovudine group (relativ e risk, 1.39; CI, 0.5 to 3.8). The rate of decline in CD4 lymphocyte c ounts was significantly slower in the zalcitabine group than in the zi dovudine group (-0.08 cells/day compared with -0.17 cells/day). Patien ts in the zalcitabine group had gained an average of 0.5 kg at week 20 and 0.4 kg at week 24, whereas patients in the zidovudine group had l ost an average of 1.8 kg at week 20 and 2.4 kg at week 24 (P = 0.04 an d P = 0.05, respectively). Moderate to severe peripheral neuropathy an d ulcerative stomatitis occurred in 10 and 9 patients, respectively, i n the zalcitabine group. Conclusions: The sample size for this study w as smaller than planned, and no differences in survival and clinical e nd points were found. Slower rates of decline in CD4 lymphocyte counts and weight, however, were noted for the zalcitabine group.