Abstract

This chapter focuses on the use of simian immunodeficiency virus (SIV) infection of macaques as animal model of human immunodeficiency virus (HIV) infection. Rhesus macaques (Macaca mulatta), or cynomolgus macaques (M. fascicularis) are mostly used in this model. Although juvenile and adult macaques are suitable for short-term treatment aimed at preventing or modulating infection, the use of newborn macaques is more practical to evaluate reliably the efficacy of prolonged drug therapy on disease progression. Animal housing and laboratory facilities need to comply with biosafety level 2 requirements for the containment of infectious biohazardous agents and the macaques need to be simian type D retrovirus-free and SIV-seronegative. For virus inoculation and sample collection, animals are usually immobilized with ketamine HCI 10–15 mg/kg injected intramuscularly. A major advantage of SIV infection of macaques is that the efficacy of antiviral drugs can be evaluated thoroughly, not only by measuring reduction in virus levels, but also by monitoring disease progression. Additionally, the laboratory and clinical parameters, which are used to monitor the course of SIV infection in macaques are very similar or identical to those which are used for HIV infection of humans. The chemoprophylactic efficacy of an antiviral compound is determined by its ability to prevent SIV infection following inoculation with a virus dose sufficient to cause persistent infection in untreated control macaques.

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