title: Effect of dosing frequency on ZDV prophylaxis in macaques infected with simian immunodeficiency virus.
abstract: 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.
authors.affiliation: University of Washington, Regional Primate Research Center, Seattle, Washington.
authors.forename: C C
authors.initials: CC
authors.lastname: Tsai
authors.forename: K E
authors.initials: KE
authors.lastname: Follis
authors.forename: R F
authors.initials: RF
authors.lastname: Grant
authors.forename: R E
authors.initials: RE
authors.lastname: Nolte
authors.forename: C R
authors.initials: CR
authors.lastname: Bartz
authors.forename: R E
authors.initials: RE
authors.lastname: Benveniste
authors.forename: P R
authors.initials: PR
authors.lastname: Sager
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D015215:Zidovudine