Phase I Study of 2',3'-Dideoxyinosine: Experience with 19 Patients at New York University Medical Center

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddl) in 19patients with AIDS or AIDS-related complex in order (1) to establish the maxi-mal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had re-ceived zidovudine therapy previously. The maximal tolerated dosage of ddl was found to be '\)12 mg/Ikg-d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levelsof p24 antigen. The major toxic effects of ddl are different from those associated with zidovudine. At the proper dosage, ddl may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treat-ment of patients who cannot tolerate zidovudine. The chronic administration of the dideoxynucleo-side analogue zidovudine has been shown to be clin