Format

Send to

Choose Destination
See comment in PubMed Commons below
J Acquir Immune Defic Syndr. 2013 Apr 1;62(4):367-74. doi: 10.1097/QAI.0b013e31827b55f1.

HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro.

Author information

1
Department of Clinical Virology, Gilead Sciences, Inc, Foster City, CA.

Abstract

BACKGROUND:

HIV-2 is susceptible to only a subset of approved antiretroviral drugs. A single tablet regimen containing the integrase strand transfer inhibitor elvitegravir (EVG) boosted by cobicistat plus the nucleoside reverse transcriptase (RT) inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) has potent activity against HIV-1 and may have utility against HIV-2.

METHODS:

HIV-2 susceptibility to EVG, FTC, and tenofovir (TFV) and selection of resistance mutations were characterized in vitro using dose escalation and breakthrough methods. HIV-2 containing the selected mutations was constructed and phenotyped in vitro.

RESULTS:

The inhibitors EVG, FTC, and TFV had potent activity against HIV-2 with EC50 values of 1.6 nM, 0.99 μM, and 3.5 μM, respectively. In resistance selections, EVG selected E92G/Q and S147N in integrase, FTC selected M184V/I in RT, and TFV selected K65R and Y115F in RT. HIV-2 site-directed mutant (SDM) viruses with E92G and E92Q integrase mutations showed 3.7- and 16-fold reduced susceptibilities to EVG, respectively. The RT M184I and M184V SDM viruses were both highly resistant to FTC (34- and >1000-fold, respectively). The RT K65R SDM virus had 2.2- and 9.1-fold reduced susceptibilities to TFV and FTC, respectively, and the addition of Y115F to K65R further decreased susceptibility to both drugs.

CONCLUSIONS:

The antiretrovirals EVG, FTC, and TFV showed potent inhibition of HIV-1 and HIV-2 in vitro and selected analogous mutations in HIV-2 and HIV-1. This suggests that the single tablet regimen of EVG/COBI/FTC/TDF should be studied as a treatment option for HIV-2 infection and would likely select for known resistance mutations.

PMID:
23187937
DOI:
10.1097/QAI.0b013e31827b55f1
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Wolters Kluwer
    Loading ...
    Support Center