DIDANOSINE COMPARED WITH CONTINUATION OF ZIDOVUDINE IN HIV-INFECTED PATIENTS WITH SIGNS OF CLINICAL DETERIORATION WHILE RECEIVING ZIDOVUDINE - A RANDOMIZED, DOUBLE-BLIND CLINICAL-TRIAL

Objective: To determine the benefits of switching to didanosine compar ed with continuing zidovudine among patients infected with human immun odeficiency virus (HIV) who have previously used zidovudine and have s igns of clinical deterioration. Design:Randomized, double-blind, two-a rmed, parallel, comparative clinical trial with a blinded, compassiona te crossover provision at 12 weeks. Setting: Outpatient clinics at 19 tertiary care medical centers. Patients: 312 patients infected with HI V who had received zidovudine for 6 months or more, had CD4 cell count s of 300/mm(3) or less, and had signs of clinical deterioration within 12 weeks before study entry. Intervention: Peroral didanosine tablets (600 mg/d adjusted for weight, ''high dose'') or zidovudine capsules (600 mg/d). Measurements: Primary study end points were death, a new a cquired immunodeficiency syndrome (AIDS)-defining event, or the combin ation of two new or recurrent HIV-related diagnoses with a 50% decreas e in CD4 cells. Results: Switching to didanosine was associated with f ewer end points than continuing zidovudine (relative risk [RR] for zid ovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consis tent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 10 0/mm(3) or more (RR = 2.2; Cl, 1.1 to 4.4). Conclusions: This study sh ows a positive treatment effect for switching from zidovudine to didan osine among patients with either AIDS-related complex or AIDS and vali dates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.