Mutagenic outcome of combined antiviral drug treatment during human immunodeficiency virus type 1 replication.
The development of antiviral drug resistance is an important problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Potent antiretroviral therapy (ART) is currently used for treatment, and typically consists of at least two reverse transcriptase (RT) inhibitors. To assess the impact of combination therapy on HIV-1 mutagenesis, the mutagenic outcome of combined drug treatment was determined with several different RT drug combinations. Significant increases in HIV-1 mutant frequencies were observed with combinations of nucleoside RT inhibitors as well as in combinations where nucleoside inhibitors were used along with hydroxyurea, a drug known to deplete nucleotide pools in cells. This indicates that combinations of RT drugs can act together to further increase HIV-1 mutant frequencies, which could have important implications for virus population dynamics and could compromise drug therapy regimens.
Mansky
Louis M
LM
Department of Molecular Virology, Immunology, and Medical Genetics, 2078 Graves Hall, 333 West 10th Avenue, Ohio State University Medical Center, Columbus, OH 43210, USA. mansky.3@osu.edu
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005822:Genetic Vectors; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016296:Mutagenesis; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents