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Different Pathways Leading to Integrase Inhibitors Resistance

Eloïse Thierry1, Eric Deprez1, Olivier Delelis1

  • 1Laboratoire de Biologie et Pharmacologie Appliquée, CNRS UMR8113, Ecole Normale Supérieure de Cachan, Université Paris-Saclay Cachan, France.

Frontiers in Microbiology
|January 27, 2017
PubMed

Integrase strand-transfer inhibitors (INSTIs), such as raltegravir (RAL), elvitegravir, or dolutegravir (DTG), are efficient antiretroviral agents used in HIV treatment in order to inhibit retroviral integration. By contrast to RAL treatments leading to well-identified mutation resistance pathways at the integrase level, recent clinical studies report several cases of patients failing DTG treatment without clearly identified resistance mutation in the integrase gene raising questions for the mechanism behind the resistance. These compounds, by impairing the integration of HIV-1 viral DNA into the host DNA, lead to an accumulation of unintegrated circular viral DNA forms. This viral DNA could be at the origin of the INSTI resistance by two different ways. The first one, sustained by a recent report, involves 2-long terminal repeat circles integration and the second one involves expression of accumulated unintegrated viral DNA leading to a basal production of viral particles maintaining the viral information.

Keywords:
HIV-1integrasestrand-transfer inhibitorsunintegrated viral DNAviral resistance

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