title: Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors.
abstract: 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.
authors.affiliation: Institute of Virology, University of Erlangen-Nürnberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Uberla
authors.forename: C
authors.initials: C
authors.lastname: Stahl-Hennig
authors.forename: D
authors.initials: D
authors.lastname: Böttiger
authors.forename: K
authors.initials: K
authors.lastname: Mätz-Rensing
authors.forename: F J
authors.initials: FJ
authors.lastname: Kaup
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: W A
authors.initials: WA
authors.lastname: Haseltine
authors.forename: B
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: G
authors.initials: G
authors.lastname: Hunsmann
authors.forename: B
authors.initials: B
authors.lastname: Oberg
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004195:Disease Models, Animal; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D011725:Pyridines / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors; D015302:Simian Immunodeficiency Virus / Q000201:enzymology; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; C095511:trovirdine