Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once daily

In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was administered once daily to 36 patients with AIDS or AIDS-related complex for up to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients previously treated with zidovudine had developed hematologic intolerance. The maximal tolerated dosage of ddI was 12 mg/(kg.d); dose-limiting toxicities were pancreatitis and peripheral neuropathy. Other toxicities included elevation in hepatic transaminase levels, rash, cardiac conduction abnormality, and asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks of treatment showed improvement in constitutional symptoms and significant weight gain. In patients treated with ddI, the mean number of CD4+ lymphocytes increased from 124/mm3 at baseline to 199/mm3 at 24 weeks (P = .0027) and the mean leukocyte count, total lymphocyte count, and hemoglobin level showed increases (all P less than .01) after 12 weeks. Serum levels of viral p24 antigen decreased greater than or equal to 50% in 14 of 19 assessable patients. No differences between the responses of patients previously treated with zidovudine and those of zidovudine-naive patients were observed. These results indicate that ddI has significant antiretroviral activity in vivo and a toxicity profile different from that of zidovudine.