Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors.
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.
Uberla
K
K
Institute of Virology, University of Erlangen-Nürnberg, Germany.
Stahl-Hennig
C
C
Böttiger
D
D
Mätz-Rensing
K
K
Kaup
F J
FJ
Li
J
J
Haseltine
W A
WA
Fleckenstein
B
B
Hunsmann
G
G
Oberg
B
B
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
D000998:Antiviral Agents; D017931:DNA Primers; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; C095511:trovirdine