Effect of dosing frequency on ZDV prophylaxis in macaques infected with simian immunodeficiency virus.
The effect of dosing frequency on zidovudine (ZDV) prophylaxis against simian immunodeficiency virus (SIV) infection was examined in long-tailed macaque monkeys (Macaca fascicularis). The results indicate that dosing frequency is extremely important for drug efficacy. The monkeys were divided into three groups based on dosing frequencies of 6-, 8-, or 12-h intervals. All were given a total daily dose of 100 mg/kg of ZDV. The drug was administered subcutaneously starting 24 h before SIV inoculation, and treatment continued for an additional 28 days. With the total daily dose held constant, ZDV was most therapeutic when administered at 12-h intervals, less effective at 8-h intervals, and least effective at 6-h intervals. These results indicate that early ZDV treatment based on infrequent but high dosages may increase the antiretroviral effect of the drug. These findings could serve as a model for ZDV chemoprophylaxis in humans. In cases involving accidental exposure to SIV or human immunodeficiency virus (HIV-1 or HIV-2), immediate, high-dosage therapies may be most therapeutic.
Tsai
C C
CC
University of Washington, Regional Primate Research Center, Seattle, Washington.
Follis
K E
KE
Grant
R F
RF
Nolte
R E
RE
Bartz
C R
CR
Benveniste
R E
RE
Sager
P R
PR
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D016131:Lymphocyte Subsets / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy / Q000382:microbiology; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D000914:Antibodies, Viral; D017931:DNA Primers; D015215:Zidovudine