AIDS THERAPIES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A great deal of our understanding of the viruses that cause AIDS as well as the disease itself has been acquired through study of nonhuman primate (NHP) models. Numerous similarities between human HIV/AIDS and simian SIV/AIDS provide the basis to experimentally study virus pathogenicity and disease intervention strategies in simian models with direct implications for the human disease understanding and treatment. Further, the importance of using NHP for preclinical drug testing to confirm efficacy against a highly similar virus and disease is recognized as the quickest experimental method to move these much need therapeutic agents into human clinical trials. Preclinical trials have been deemed a necessary step in the approval process for candidate human drugs. The FDA's so called "two animal rule" applies to candidate AIDS drugs whereby safety and efficacy demonstrated in two animal models could result in immediate licensure for human use. NHP are recognized as the ideal second or non-rodent animal model. This is particularly true for immune system attaching infectious agents that infect by traversing mucous membranes as does HIV. Prototypical studies involve 4 to six groups of 5 or 6 animals. Each group is challenged by a proven virus stock after or concurrently with antiviral (usually delivered in multiple concentrations to each treated group) or mock-treatment. Drug efficacies are determined by the outcomes of the infectious challenges and the degree -with respect to the mock-treated controls that the virus infections are limited. Additionally, local and systemic candidate drug toxicity are evaluated during efficacy trials.