A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

ABSTRACT

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.