THE USE OF SIV-INFECTED RHESUS-MONKEYS FOR THE PRECLINICAL EVALUATION OF AIDS DRUGS AND VACCINES

Macaque monkeys infected with the simian immunodeficiency virus (SIV) can be used for preclinical testing of drugs and vaccines against acquired immunodeficiency syndrome (AIDS) as well as for the study of AIDS pathogenesis. A number of pathogenic SIV strains that have been well characterized molecularly and biologically are available for animal infection studies. Data generated from in vitro drug sensitivity assays have established, for many classes of compounds, a similar degree of antiviral efficacy against both HIV-1 and the SIVs, although some examples of selective inhibitors of HIV-1 now are known. A number of virus and host parameters have been defined that provide suitable biological endpoints for in vivo efficacy studies during acute and chronic infection of macaque monkeys. Vaccine studies in SIV-infected monkeys have provided hope that immune protection against lentiviruses is possible; SIV systems are playing a major role in systematically comparing various vaccine strategies to determine correlates of immunity and the protection required for mucosal versus parenteral routes of infection. Societal pressures and the expanding AIDS epidemic will continue to encourage early testing of experimental drugs and vaccines in human clinical trials, however, as more data validating the SIV system are generated, the utility of the SIV model in preclinical development likely will become apparent. Impetus to evaluate therapies in this model system will increase if the current method of testing in humans does not identify more effective AIDS therapies in the near future.