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

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

Author information

1
1 Division of Infectious Diseases, Department of Medicine, Stanford University , Stanford, California.
2
2 Department of Pathology, Stanford University , Stanford, California.
3
3 Department of Microbiology and Immunology, Stanford University , Stanford, California.
4
4 Kaiser Permanente Medical Care Program-Northern California , Oakland, California.

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.

PMID:
27009474
PMCID:
PMC4931751
DOI:
10.1089/AID.2016.0038
[Indexed for MEDLINE]
Free PMC Article

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