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

Macaque monkeys infected with the simian immunodeficiency virus (SIV) can be used for preclinical testing of drugs and vaccines against acqu ired 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 in fection studies. Data generated from in vitro drug sensitivity assays have established, for many classes of compounds, a similar degree of a ntiviral efficacy against both HIV-1 and the SIVs, although some examp les 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 infec tion 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 vari ous vaccine strategies to determine correlates of immunity and the pro tection required for mucosal versus parenteral routes of infection. So cietal pressures and the expanding AIDS epidemic will continue to enco urage early testing of experimental drugs and vaccines in human clinic al trials, however, as more data validating the SIV system are generat ed, the utility of the SIV model in preclinical development likely wil l become apparent. Impetus to evaluate therapies in this model system will increase if the current method of testing in humans does not iden tify more effective AIDS therapies in the near future.