Zalcitabine Compared with Zidovudine in Patients with Advanced HIV-1 Infection Who Received Previous Zidovudine Therapy

15 May 1993 | Volume 118 Issue 10 | Pages 762-769

Objective: To evaluate the safety and efficacy of zalcitabine (also known as dideoxycytidine [ddC]) in patients with advanced human immunodeficiency virus (HIV) infection.

Design: Open-label, randomized study.

Setting: AIDS Clinical Trials Units, university-affiliated medical centers, and private practice groups.

Patients: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex who had tolerated zidovudine for 48 weeks or more.

Intervention: Fifty-nine patients received zidovudine (500 to 1200 mg/d) and 52 patients received zalcitabine (2.25 mg/d).

Measurements: The primary end points were survival and time to an AIDS-defining event or death.

Results: Because significantly more patients withdrew from zidovudine therapy, the median duration of treatment was greater in the zalcitabine group than 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 the 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 81% for the zalcitabine group and 75% for the zidovudine group (relative risk, 1.39; CI, 0.5 to 3.8). The rate of decline in CD4 lymphocyte counts was significantly slower in the zalcitabine group than in the zidovudine group ( –0.08 cells/day compared with –0.17 cells/day). Patients 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 lost an average of 1.8 kg at week 20 and 2.4 kg at week 24 (P = 0.04 and P = 0.05, respectively). Moderate to severe peripheral neuropathy and ulcerative stomatitis occurred in 10 and 9 patients, respectively, in the zalcitabine group.

Conclusions: The sample size for this study was smaller than planned, and no differences in survival and clinical end points were found. Slower rates of decline in CD4 lymphocyte counts and weight, however, were noted for the zalcitabine group.

*Other participants are listed in the Appendix.

For current author addresses, see end of text.

Author and Article Information

From the University of Miami School of Medicine, Miami, Florida; OakLawn Physicians Group, Dallas, Texas; Davies Medical Center, San Francisco, California; Mount Zion Hospital and Medical Center, University of California, San Francisco, California; Graduate Hospital, Philadelphia, Pennsylvania; University of Cincinnati Medical Center, Cincinnati, Ohio; Albany Medical College, Albany, New York; Hoffmann-La Roche Inc., Nutley, New Jersey.
Requests for Reprints: Margaret A. Fischl, MD, University of Miami School of Medicine, Department of Medicine, R-60A, P.O. Box 016960, Miami, FL 33101.
Grant Support: In part by the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and Hoffmann-La Roche, Inc.