Effect of dosing frequency on AZT prophylaxis against SIV infection in cynomolgus monkeys.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Effect of dosing frequency on AZT prophylaxis against SIV infection in cynomolgus monkeys.

Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 107. Unique Identifier : AIDSLINE PRIM10/93200943
Tsai CC; Follis KE; Grant R; Nolte RE; Bartz C; Benveniste RE; Sager PR; Regional Primate Research Center, University of Washington,; Seattle 98195.

Abstract: Early AZT treatment has been shown to prolong life for certain HIV-infected persons if taken before the symptoms of AIDS develop. However, it is still uncertain whether dosing frequency of AZT affects anti-HIV activity. Therefore, we studied the effects of dosing frequency on AZT prophylaxis against simian immunodeficiency virus (SIV) infection in cynomolgus monkeys as a primate model for HIV. Dosing frequencies of either 2, 3, or 4 times daily (b.i.d., t.i.d., or q.i.d.) for a total of 100 mg/kg/day AZT were given by subcutaneous injection to three groups of six monkeys each. Treatment was initiated 24 hr prior to intravenous virus challenge and was continued for 28 days. Six additional monkeys served as untreated infected controls. Virologic, immunologic, and clinical parameters were monitored for 240 days post-challenge. In the b.i.d. dosing group, one treated monkey showed no evidence of viral infection, and 4 of 6 treated monkeys had persistently low virus levels. In the t.i.d. dosing group, 2 of 6 treated monkeys had persistently low virus burden. Monkeys in the q.i.d. dosing group and the remaining AZT-treated monkeys, had virus levels similar to the untreated infected controls. All AZT treated monkeys showed hematologic toxicity including decreased hemoglobin and granulocytopenia; however, normal levels were regained two weeks after treatment withdrawal. The results of this study indicate that the infrequent dosage regimen increased the antiretroviral activity of AZT without increasing toxicity. These findings suggest that chemoprophylaxis in humans following accidental exposure to HIV may be most effective when AZT is immediately and consistently administered using an infrequent but higher dosage regimen. Laboratory monitoring should be closely followed to determine the efficacy and duration of AZT therapy.

Keywords: Animal Comparative Study Drug Administration Schedule Macaca fascicularis Simian Acquired Immunodeficiency Syndrome/*PREVENTION & CONTROL *SIV Time Factors Zidovudine/ADMINISTRATION & DOSAGE/TOXICITY/THERAPEUTIC USE ABSTRACT
930630
M9361077

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1993. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1993. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .