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The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro

Francesco Saladini, Alessia Giannini, Adele Boccuto, Diletta Tiezzi, Ilaria Vicenti, Maurizio Zazzi

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Abstract

: The HIV-1 integrase E157Q natural polymorphism has been reported to cause one case of raltegravir (RAL) and dolutegravir (DTG) failure. Six recombinant viruses were constructed containing integrase from clinical HIV-1 isolates found to harbour E157Q as the only integrase strand inhibitor (INSTI) resistance-related mutation. Phenotypic analysis showed that E157Q results in minimal changes in RAL and DTG susceptibility. Together with data retrieved from the Stanford HIV database, our results indicate that E157Q is not a relevant INSTI resistance mutation per se. The previously reported case of E157Q-based resistance must have resulted from combined as yet unidentified integrase polymorphisms.

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What this paper is about

: The HIV-1 integrase E157Q natural polymorphism has been reported to cause one case of raltegravir (RAL) and dolutegravir (DTG) failure. Six recombinant viruses were constructed containing integrase from clinical HIV-1 isolates found to harbour E157Q as the only integrase strand inhibitor (INSTI) resistance-related mutation. Phenotypic analysis showed that E157Q results in minimal changes in RAL and DTG susceptibility. Together with data retrieved from the Stanford HIV database, our results indicate that E157Q is not a relevant INSTI resistance mutation per se. The previously reported case of E157Q-based resistance must have resulted from combined as yet unidentified integrase polymorphisms.

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Available abstract

: The HIV-1 integrase E157Q natural polymorphism has been reported to cause one case of raltegravir (RAL) and dolutegravir (DTG) failure. Six recombinant viruses were constructed containing integrase from clinical HIV-1 isolates found to harbour E157Q as the only integrase strand inhibitor (INSTI) resistance-related mutation. Phenotypic analysis showed that E157Q results in minimal changes in RAL and DTG susceptibility. Together with data retrieved from the Stanford HIV database, our results indicate that E157Q is not a relevant INSTI resistance mutation per se. The previously reported case of E157Q-based resistance must have resulted from combined as yet unidentified integrase polymorphisms.

Key concepts: Raltegravir, Dolutegravir, Integrase inhibitor, Integrase, Virology, Human immunodeficiency virus (HIV), In vitro, Medicine

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The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro — Research Paper | ScholarLens