We conducted a Phase I open-label trial of
2',3'-dideoxyinosine (ddI) for the treatment of the
acquired immunodeficiency syndrome (
AIDS) and severe
AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with
AIDS and 17 with
AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of
body weight per day. Of the 17 patients previously treated with
zidovudine, 13 had had hematologic side effects. The maximal tolerated dose of oral ddI was estimated to be 20.4 mg per kilogram per day.
Pancreatitis and
peripheral neuropathy were the major dose-limiting toxic effects. Other toxic effects included elevations in hepatic
transaminase levels, abnormalities in cardiac conduction,
rash, and asymptomatic elevations in serum
urate levels and the
creatine kinase fraction from skeletal muscle. Treatment with ddI was associated with an increase in the mean number of CD4 lymphocytes from 125 per cubic millimeter at base line to 182 per cubic millimeter after 10 weeks (P = 0.005). There were also increases after 12 weeks in the mean total lymphocyte count (from 0.8 to 1.2 x 10(9) per liter) and the mean
hemoglobin level (from 12.9 to 14.1 g per deciliter) (both P less than 0.01). The amount of human immunodeficiency virus p24
antigen decreased by more than 50 percent in 14 of 19 patients with detectable
antigen. No differences in response were observed between patients previously treated with
zidovudine and those never treated with the
drug. We conclude that ddI has antiretroviral activity in patients with
AIDS or
AIDS-related complex and that the toxicity of ddI differs from that of
zidovudine. However, controlled trials are necessary to evaluate the efficacy of ddI.