LONG-TERM TOXICITY ACTIVITY PROFILE OF 2',3'-DIDEOXYINOSINE IN AIDS OR AIDS-RELATED COMPLEX

To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine (ddl), a potent inhibitor of human immunodeficiency virus (HIV) replication, in vitro. 58 patients with AIDS or AIDS-related complex were studied with additional reference to the effect of previous treatment with zidovudine, and the effect of ddl on HIV-induced cognitive dysfunction. Doses above 9·6 mg/kg per day of ddl were frequently associated with toxicity (peripheral neuropathy, pancreatitis, or hepatitis). Doses of 9·6 mg/kg per day or below were well tolerated for up to 21 months. A subset of patients receiving 3·2-9·6 mg/kg per day of ddl had long-term immunological improvement and reduction of serum HIV p24 antigen. Immunological changes were especially seen in patients who had little previous zidovudine therapy. 5 patients with HIV-induced cognitive impairment improved with ddl. Thus, ddl may have anti-HIV activity at doses which are tolerated for long-term therapy, although pancreatitis could be a life-threatening complication. © 1990.