Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.
Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV-2 and antibody received ddC prophylaxis prior to challenge with virus and continued to receive ddC therapy for up to 28 days postchallenge. All monkeys treated with a continuous intravenous dose of ddC, which maintained plasma concentrations of ddC at levels known to inhibit SRV-2 in vitro, developed dose-related toxic effects, including leukopenia, anemia, lethargy, and decreased appetite. Monkeys treated with a daily bolus injection of ddC experienced more severe toxic effects than those on the continuous intravenous regimen, including exfoliative dermatitis and peripheral neuropathy. At the concentrations of ddC administered, no significant inhibition of SRV-2 replication was detected in naturally infected macaques. However, a prophylactic regimen of ddC did have an inhibitory effect on SRV-2. Our findings suggest that ddC may be valuable as a short-term prophylactic treatment rather than as a long-term therapy.
Tsai
C C
CC
Regional Primate Research Center, University of Washington, Seattle 98195.
Follis
K E
KE
Yarnall
M
M
Blakley
G A
GA
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D005455:Fluorescent Antibody Technique; D008254:Macaca nemestrina; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000473:pathology; D015301:Retroviruses, Simian / Q000187:drug effects* / Q000276:immunology; D016047:Zalcitabine / Q000627:therapeutic use* / Q000633:toxicity
D000956:Antigens, Viral; D016047:Zalcitabine