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 (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.
Yarchoan
R
R
Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892.
Pluda
J M
JM
Thomas
R V
RV
Mitsuya
H
H
Brouwers
P
P
Wyvill
K M
KM
Hartman
N
N
Johns
D G
DG
Broder
S
S
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
D015215:Zidovudine; D016049:Didanosine