Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 218, Issue 11, Pages 1773-1776Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy428
Keywords
integrase inhibitors; bictegravir; cabotegravir; dolutegravir; integrase resistance testing; phenotype
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Funding
- Genome Canada
- Genome BC
- Canadian Institutes of Health Research, via the large-scale HIV 142 project
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Bictegravir (BIC) and cabotegravir (CAB) are the latest available HIV integrase inhibitors in clinical trials. The combination of major integrase inhibitor substitutions G140S/Q148H has been shown to confer high-level resistance to the approved integrase inhibitors raltegravir (RAL) and elvitegravir (EVG) but not necessarily dolutegravir (DTG). We assayed recombinant viruses made from patient-derived RNA extracts for resistance phenotype for a panel of viruses containing G140S/Q148H with additional accessory substitutions. The accumulation of multiple integrase substitutions confers high-level resistance to all 5 integrase inhibitors. There is extensive cross-resistance between DTG, BIC, and CAB (r = 0.96-0.97).
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