Animal Model for the Therapy of Acquired Immunodeficiency Syndrome with Reverse Transcriptase Inhibitors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (18), p.8210-8214
• Main Authors: Uberla, Klaus, Stahl-Hennig, Christiane, Bottiger, Disa, Matz-Rensing, Kerstin, Kaup, Franz J.
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; AIDS; AIDS/HIV; Amino Acid Sequence; Animal models; Animals; Antibodies; Antigens; Antiviral Agents - therapeutic use; Antivirals; Base Sequence; Cell Line; Disease Models, Animal; DNA Primers; Dosage; Drug resistance; Drugs; HIV; HIV 1; HIV Reverse Transcriptase; HIV-1 - enzymology; Human immunodeficiency virus; human immunodeficiency virus 1; Infections; Laboratory animals; Macaca fascicularis; Macaca mulatta; Medical research; Medicin och hälsovetenskap; Molecular Sequence Data; Monkeys & apes; Pyridines - therapeutic use; Reverse Transcriptase Inhibitors; simian immunodeficiency virus; Simian Immunodeficiency Virus - enzymology; Viruses; Zidovudine - therapeutic use
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.18.8210

The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is the major target for antiretroviral therapy of the acquired immunodeficiency syndrome (AIDS). While some inhibitors exhibit activity against most retroviral RTs, others are specific for the HIV-1 enzyme. To develop an animal model for the therapy of the HIV-1 infection with RT inhibitors, the RT of the simian immunodeficiency 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 HIV-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 study the in vivo efficacy of new RT inhibitors, the emergence and reversal of drug resistance, the therapy of infections with drug-resistant viruses, and the efficacy of combination therapy.