The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions.
It is generally accepted that the fitness cost of resistance mutations plays a role in the persistence of transmitted drug-resistant human immunodeficiency virus type 1 and that mutations that confer a high fitness cost are less able to persist in the absence of drug pressure. Here, we show that the fitness cost of reverse transcriptase (RT) mutations can vary within a 72-fold range. We also demonstrate that the fitness cost of M184V and K70R can be decreased or enhanced by other resistance mutations such as D67N and K219Q. We conclude that the persistence of transmitted RT mutants might range widely on the basis of fitness and that the modulation of fitness cost by mutational interactions will be a critical determinant of persistence.
Cong
Mian-er
ME
Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
Heneine
Walid
W
García-Lerma
J Gerardo
JG
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D015658:HIV Infections / Q000635:transmission / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase