Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility

AIDS Res Hum Retroviruses. 2016 Jul;32(7):702-4. doi: 10.1089/AID.2016.0038. Epub 2016 Apr 19.

Abstract

The integrase strand transfer inhibitor (INSTI)-resistance mutations Q148H/K/R are arguably the most important INSTI-resistance mutations as they represented the first step to high-level dolutegravir cross-resistance. We describe an individual with transmitted four-class drug resistance whose virus sequence had the previously uncharacterized mutation Q148N. Infectious molecular HIV-1 clones containing Q148N alone and in combination with G140S demonstrated ∼2.4-4.5 reduced elvitegravir susceptibility depending on the virus's genetic context but retained susceptibility to raltegravir and dolutegravir. This level of reduced elvitegravir susceptibility is lower than that observed with Q148H/K/R and in fact the infected individual responded to an initial treatment regimen containing tenofovir/emtricitabine/elvitegravir/cobicistat. Q148N was associated with a higher replication capacity than Q148H, suggesting that this mutation may be more fit in the absence of selective INSTI therapy.

MeSH terms

  • Amino Acid Substitution*
  • Drug Resistance, Viral*
  • HIV Infections / virology
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation, Missense*
  • Quinolones / pharmacology*

Substances

  • HIV Integrase Inhibitors
  • JTK 303
  • Quinolones
  • HIV Integrase