Preliminary analysis of a completed phase III study comparing two antiretroviral drugs shows that didanosine (ddI), at a dose of 500 mg/day, was more efficacious than zidovudine (ZDV; AZT) in slowing the progression of HIV disease in persons who had tolerated more that 16 weeks of ZDV therapy. This benefit was seen in a subgroup of patients who entered the study with AIDS-Related Complex (ARC) or asymptomatic HIV infection, but not in those patients who had AIDS. No difference in terms of survival was seen among the study participants. The study also showed that persons receiving ddI, at a dose of either 500 mg/day or 750 mg/day, generally had higher numbers of CD4+ blood cells during the study as compared to those receiving ZDV.
Called ACTG 116-B/117, this randomized, double-blind clinical trial compared the efficacy and toxicity of two doses of ddI (500 mg/day and 750 mg/day) and one dose of ZDV (600 mg/day) in persons with AIDS, ARC, or asymptomatic HIV disease. Prior to enrolling in the study, all participants had tolerated ZDV therapy for more than 16 weeks.
The trial was designed to determine whether progression of HIV disease could be more effectively slowed by continuing ZDV therapy or by switching to ddI. Progression of HIV disease was evaluated in terms of new AIDS-defining events, or deaths, that occurred during the study. The duration of prior ZDV therapy did not influence the relative efficacy of ddI to ZDV in this study.
Investigators also compared side effects, or toxicities, of the two different doses of ddI and ZDV. They reported no significant difference among the treatment groups with regard to development of peripheral neuropathy (pain or numbness in the feet and/or legs). Inflammation of the pancreas (pancreatitis) was most commonly observed in patients receiving ddI at a dose of 750 mg/day. Patients receiving ZDV were more apt to develop lowered red and white blood cell counts that those receiving ddI.
The study, which began in October 1989, was conducted at 33 sites of the NIAID-supported AIDS Clinical Trials Group (ACTG), 6 regional centers funded by the National Hemophilia Foundation, and 4 sites supported by Bristol-Myers Squibb Company, the manufacturers of ddI. Enrollment of 913 participants ended in April 1991, and follow-up of participants was discontinued in November 1991. Burroughs Wellcome provided ZDV for the study.
Prepared by: Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892