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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.

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.

SUBMITTER: Hachiya A 

PROVIDER: S-EPMC5527620 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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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.

Hachiya Atsuko A   Kirby Karen A KA   Ido Yoko Y   Shigemi Urara U   Matsuda Masakazu M   Okazaki Reiko R   Imamura Junji J   Sarafianos Stefan G SG   Yokomaku Yoshiyuki Y   Iwatani Yasumasa Y  

Antimicrobial agents and chemotherapy 20170725 8

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 a  ...[more]

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