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Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.

Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.
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Hachiya A, Kirby KA, Ido Y, Shigemi U, Matsuda M, Okazaki R, Imamura J, Sarafianos SG, Yokomaku Y, Iwatani Y,


Hachiya A, Kirby KA, Ido Y, Shigemi U, Matsuda M, Okazaki R, Imamura J, Sarafianos SG, Yokomaku Y, Iwatani Y, (click to view)

Hachiya A, Kirby KA, Ido Y, Shigemi U, Matsuda M, Okazaki R, Imamura J, Sarafianos SG, Yokomaku Y, Iwatani Y,

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Antimicrobial agents and chemotherapy 2017 07 2561(8) pii 10.1128/AAC.00315-17

Abstract

A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.

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