Skip Navigation LinksHome > April 1, 2013 - Volume 62 - Issue 4 > HIV-2 Antiviral Potency and Selection of Drug Resistance Mut...
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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31827b55f1
Basic and Translational Science

HIV-2 Antiviral Potency and Selection of Drug Resistance Mutations by the Integrase Strand Transfer Inhibitor Elvitegravir and NRTIs Emtricitabine and Tenofovir In Vitro

Andreatta, Kristen MS; Miller, Michael D. PhD; White, Kirsten L. PhD

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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.

© 2013 Lippincott Williams & Wilkins, Inc.


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