THY LIV-SCID-HU MICE - A SYSTEM FOR INVESTIGATING THE IN-VIVO EFFECTSOF MULTIDRUG THERAPY ON PLASMA VIREMIA AND HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN LYMPHOID-TISSUES/

Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-h u mice were used to evaluate the in vivo efficacy of antiretroviral dr ugs, Ritonavir treatment alone initially suppressed plasma viremia, bu t the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, sh owing that the therapy did not completely suppress HIV infection in th e thymic implant, When thy/liv-SCID-hu mice were treated with a combin ation of zidovudine, lamivudine, and ritonavir immediately after inocu lation with HIV, cocultures of the thymic implants remained negative f or HIV even 1 month after therapy was discontinued, suggesting that ac ute treatment can prevent the establishment of HIV infection, Thus, th ese modified thy/liv-SCID-hu mice should prove to be a useful system f or evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.