title: Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS-related complex.
abstract: To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine (ddI), 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 ddI on HIV-induced cognitive dysfunction. Doses above 9.6 mg/kg per day of ddI 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 ddI 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 ddI. Thus, ddI may have anti-HIV activity at doses which are tolerated for long-term therapy, although pancreatitis could be a life-threatening complication.
authors.affiliation: Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892.
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
authors.forename: J M
authors.initials: JM
authors.lastname: Pluda
authors.forename: R V
authors.initials: RV
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Mitsuya
authors.forename: P
authors.initials: P
authors.lastname: Brouwers
authors.forename: K M
authors.initials: KM
authors.lastname: Wyvill
authors.forename: N
authors.initials: N
authors.lastname: Hartman
authors.forename: D G
authors.initials: DG
authors.lastname: Johns
authors.forename: S
authors.initials: S
authors.lastname: Broder
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology; D000386:AIDS-Related Complex / Q000188:drug therapy* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D050378:T-Lymphocytes, Regulatory; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D015215:Zidovudine; D016049:Didanosine