USE OF STANDARDIZED SCID-HU THY LIV MOUSE MODEL FOR PRECLINICAL EFFICACY TESTING OF ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 COMPOUNDS/

We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for t he prophylactic administration of antiviral compounds and for evaluati on of the antiviral effect in vivo. Endpoint analyses included quantit ation of viral load by intracellular p24 enzyme-linked immunosorbent a ssay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4(+) and CD8(+) cells, and cocultivati on for-the isolation of virus. Efficacy tests in this model are demons trated with the nucleoside analogs zidovudine and dideoxyinosine and w ith the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical p rioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determi nation of appropriate combination therapy in vivo.