A SIMPLE AND RAPID METHOD FOR PRELIMINARY EVALUATION OF IN-VIVO EFFICACY OF ANTI-HIV COMPOUNDS IN MICE

In vivo efficacy of anti-HIV compounds is affected by various factors such as bioavailability, metabolism, clearance, and toxicity. Here we report a simple and rapid method that might be useful for preliminary evaluation of in vivo efficacy of anti-HIV compounds. MT-4 cells carry ing proviral HTLV-1 were infected with HIV-1 in vitro and injected int o the peritoneal cavity of SCID mice or BALB/c mice. Inoculated cells survive for 1-2 days, and support one to two cycles of viral replicati on which can be monitored by RT activity or p24 content in the superna tants of peritoneal wash fluids. Test compounds were administered eith er orally or subcutaneously. AZT, DDC and DDI, the nucleoside-type RT inhibitors currently in clinical use, all showed potent anti-HIV-l act ivities in this mouse/MT-4 assay. HEPT (E-EBUdM), a non-nucleoside RT inhibitor, also showed potent anti-HIV-1 activity in vivo, whereas TIB O (R 82913), another non-nucleoside RT inhibitor, was less active. In protease inhibitors KNI-272 and Ro 31-8959 showed good in vivo activit ies, while KNI-144, a compound closely related to KNI-272, showed poor in vivo activity. This mouse/MT-4 assay, although having a number of shortcomings as an animal model for HIV-1 infection, may be of some pr actical utility for preliminary evaluation of in vivo efficacy of pote ntial anti-HIV compounds.