The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis

Development of anti-retroviral regimens with enhanced efficacy against brai n HIV-1 is essential if viral eradication is to be achieved. To address thi s, a severe combined immune deficiency mouse model of HIV-1 encephalitis wa s used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected h uman monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disea se. Drugs were administered at the time of MDM inoculation and continued un til sacrifice. Immunohistochemical tests evaluated ongoing viral replicatio n, glial immunity, and neuronal survival. Treatment with ddl/d4T decreased the numbers of infected cells by 75%, while ddl/d4T/amprenavir or ZDV/3TC/A BC diminished infection by 98%. Triple drug regimens decreased astrogliosis by greater than or equal to 25%. This small-animal model may be used to sc reen drug regimens that affect ongoing HIV-1 replication within its brain s anctuary, (C) 2001 Academic Press.