Treatment of HIV Disease In Vivo Efficacy Evaluations

This service provides evaluation of products in animal efficacy models. A product must demonstrate a potent and selective activity profile in vitro against the virus strain used in the model prior to its acceptance as a candidate for this service. Studies to determine optimal routes and schedules of drug administration can be performed.

SCID-hu Thy/Liv Mouse Model

• Severe-combined immunodeficient (SCID) mice are implanted with human fetal thymus and liver tissue and later inoculated with HIV. Virus replication occurs within the implanted human cells.
• HIV-1 strains commonly used in the model are NL4-3 (CXCR4-tropic) and Ba-L (CCR5-tropic).
• Antiviral efficacy is demonstrated by a reduction in virus load (p24 and RNA) and protection of the human CD4+ cells from virus-induced depletion.
• Evaluation of the product’s toxicity to the implanted tissue is performed prior to an antiviral efficacy study.
• Validation of the model has been published by Stoddart et al. in PLoS ONE 2(8): e655 (2007).

The current contractor for this service is the University of California, San Francisco.