Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Tzou, Philip L, Rhee, Soo-Yon, Descamps, Diane, Clutter, Dana S, Hare, Bradley, Mor, Orna, Grude, Maxime, Parkin, Neil, Jordan, Michael R, Bertagnolio, Silvia
et al (show 6 more authors) (2020) Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance. Journal of Antimicrobial Chemotherapy, 75 (1). 170 - 182.

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Background Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. Objectives We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. Methods To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. Results Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. Conclusions A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir.

Item Type: Article
Uncontrolled Keywords: mutation, drug resistance, hiv-1, integrase inhibitors, surveillance, medical
Depositing User: Symplectic Admin
Date Deposited: 09 Dec 2019 10:36
Last Modified: 19 May 2022 05:10
DOI: 10.1093/jac/dkz417
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