Acute Infection of Cynomolgus Monkeys with Simian Immunodeficiency Virus (SIVSM) as a Model to Evaluate Antiviral Compounds. Effects of 3′-Azido, 3′-Deoxythymidine, Foscarnet and 2′,3′-Dideoxycytidine

Abstract

Screening of compounds with potential use in the treatment of human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) can currently be made in cell culture systems, but there is a need for relevant animal models. We have infected cynomolgus monkeys with simian immunodeficiency virus of sooty mangabey origin (SIV_SM) and investigated the influence of multiplicity of infection (MOI) and the effects of three different anti-HIV compounds, 3′-azido-3′-deoxythymidine (AZT), foscarnet (PFA) and 2′,3′-dideoxycytidine (ddC) on the acute infection. To secure a maximal effect of treatment this was started 8h before challenge with SIV_SM and the drugs were given subsequently every 8h for 7–9 days. The appearance of viral antigen and antibodies in serum was determined. In control animals the mean day for SIV antigen appearance was Day 5.9 post-infection, whereas in animals treated with 3 × 25 mg kg⁻¹ day⁻¹ of AZT and 3 × 65 mg kg⁻¹ day⁻¹ of PFA there were significant delays in SIV antigen appearance of 1.0 and 3.6 days, respectively. Some delay in antigen appearance was indicated in animals treated with 3 × 0.2 mg kg⁻¹ day⁻¹ of ddC. A delayed antibody response was only seen in animals treated with PFA. Viral infection was not prevented at the multiplicity used with any of the drugs, despite treatment prior to virus inoculation. The animal model described offers attractive features for in vivo evaluation of potential anti-HIV compounds.