Effect of dosing frequency on ZDV prophylaxis in macaques infected with simian immunodeficiency virus
Tsai, C.C.; Follis, K.E.; Grant, R.F.; Nolte, R.E.; Bartz, C.R.; Benveniste, R.E.; Sager, P.R.
Journal of Acquired Immune Deficiency Syndromes 6(10): 1086-1092
1993
ISSN/ISBN: 0894-9255 PMID: 8410666 Document Number: 405998
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.