Comparison of the efficacy of AZT and PMEA treatment on acute SIVMNE infection in macaques.

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Comparison of the efficacy of AZT and PMEA treatment on acute SIVMNE infection in macaques.

Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 43. Unique Identifier : AIDSLINE PRIM11/94191638
Tsai CC; Follis KE; Grant R; Sabo A; Nolte R; Bartz C; Bischofberger N; Benveniste R; University of Washington Primate Research Center, Seattle.

Abstract: The efficacy of the antiviral agents azidothymidine (AZT) and 9-(-2-phosphonylmethoxyethyl)adenine (PMEA) against SIV was compared in long-tailed macaques (Macaca fascicularis). A total of 48 macaques were used for this study and treated employing the following schedule: 18 macaques, 100 mg/kg/day AZT; 12 macaques, 20 mg/kg/day PMEA; 6 macaques, 10 mg/kg/day PMEA; and 12 macaques, infected, mock-treated controls. Macaques were pretreated for 24 h with AZT or for 48 hr with PMEA before the SIV intravenous inoculation. Each macaque was inoculated with 10 times the 50% monkey infectious dose (10 MID50 = 10(3) CCID) obtained from the same virus stock. After virus administration, the macaques were treated with AZT or PMEA for an additional 28 days. Macaques were regularly tested for virus and antibody for up to 30 weeks post-inoculation. Assays include: PBMC cocultures, PBMC PCR of SIV DNA, plasma SIV p27 and antibody levels, and lymph node biopsies. The results of AZT treatment showed that only 5.6% (1 of 18) of the macaques remained free of SIV infection. By comparison, the results of PMEA treatment demonstrated that 83% (10 of 12) of the macaques treated with 20 mg/kg/day and 50% (3 of 6) of the macaques treated with 10 mg/kg/day remained free of SIV infection. These results indicate that chemoprophylaxis with PMEA against acute SIV infection in macaques has a dramatic antiretroviral effect as compared to AZT treatment. Since SIV and HIV are closely related, this pronounced antiretroviral effect of PMEA may translate into a benefit in the treatment of AIDS.

Keywords: Acquired Immunodeficiency Syndrome/DRUG THERAPY Adenine/*ANALOGS & DERIVATIVES/THERAPEUTIC USE Animal Antiviral Agents/*THERAPEUTIC USE Comparative Study Drug Administration Schedule Human Macaca fascicularis Simian Acquired Immunodeficiency Syndrome/*DRUG THERAPY/ PREVENTION & CONTROL SIV Time Factors Zidovudine/*THERAPEUTIC USE ABSTRACT
940730
M9470880

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