ANIMAL-MODEL FOR THE THERAPY OF ACQUIRED-IMMUNODEFICIENCY-SYNDROME WITH REVERSE-TRANSCRIPTASE INHIBITORS

The reverse transcriptase (RT) of the human immunodeficiency virus typ e 1 (HIV-1) is the major target for antiretroviral therapy of the acqu ired immunodeficiency syndrome (AIDS), While some inhibitors exhibit a ctivity against most retroviral RTs, others are specific for the HIV-1 enzyme. To develop an animal model for the therapy of the HIV-1 infec tion with RT inhibitors, the RT of the simian immuno-deficiency virus (SIV) was replaced by the RT of HIV-1. Macaques infected with this SIV /HIV-1 hybrid virus developed AIDS-like symptoms and pathology, The HI V-1-specific RT inhibitor LY300046 . HCl, but not zidovudine [3'-azido -3'deoxythymidine (AZT)] delayed the appearance of plasma antigenemia in macaques infected with a high dose of the chimeric virus, Infection of macaques with the chimeric virus seems to be a valuable model to s tudy the in vivo efficacy of new RT inhibitors, the emergence and reve rsal of drug resistance, the therapy of infections with drug-resistant viruses, and the efficacy of combination therapy.