HIV mutagenesis and the evolution of antiretroviral drug resistance.
The development of antiretroviral drug resistance is a major threat to the effective treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug treatment failure is associated with accumulation of drug resistance mutations and the evolution of drug resistance. Studies from microbial systems provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Recent studies with HIV-1 have shown that drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT can increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT have been found to increase virus mutation frequencies in a multiplicative manner. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens.
Mansky
Louis M
LM
Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, Ohio State University Medical Center, 2078 Graves Hall, 333 West 10th Avenue, Columbus 43210, USA. mansky.3@osu.edu
D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects*
D019380:Anti-HIV Agents