EACS 2023: Prevalence of doravirine drug resistance in large cohort in British Columbia
1 December 2023. Related: Conference reports, Research studies, EACS 19 Warsaw 2023.
Kirk Taylor, HIV i-Base
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EACS 2023 included an oral presentation on the prevalence of mutations associated with resistance to doravirine in a large observational cohort in British Columbia.
A database reviewed almost 39,000 sequences collected since 1996 from more than 10,000 people living with HIV at the BC Centre for Excellence in HIV/AIDS.
Approximately 5400 samples were NNRTI-naive, 15,400 were NNRTI-experienced and 18,000 with an unknown NNRTI history were assumed to have started with PI- or INSTI-based ART (but not commenting on whether this was linked to baseline resistance).
Doravirine resistance was categorised based on having one or more primary or secondary major mutations or having at least 5 minor mutations (based on Stanford).
| Primary major | Y106A, Y188L, F227C/V, M230I/L, L234I, Y318F |
| Secondary major | A98G, V106M, V108L, G190E, H221Y, P225H, F227L, P236L |
| Minor mutations | V90I, K101E/H/P, K103N/R/, V106L, I135T, Y181C/I/V, E138A/G/K/Q/R, V179D/F/T, G109A/Q/S, Y188C/H, F2271, V245E, K311R |
Overall, 20% genotypes (7995/38,808) included any NNRTI resistance (including 30% of those who were NNRTI-experienced). Only 835 samples (2.2%) showed resistance to doravirine (roughly 5% of those who were NNRTI-experienced.
Of the 230 people prescribed doravirine, 32% (75/230) had previous NNRTI resistance but most switched when already undetectable and used either triple-class or four-drug combinations, with only 10/75 starting on doravirine plus two NRTIs.
The three people with virological failure had single mutations at (i) V106M, (ii) M230L and (iii) with multiple mutations at V106I/M+V108I+F227C+M230L+L234I.
Reference:
Brumme C. Prevalence and clinical impact of doravirine-associated resistance mutations in a real-world population of NNRTI-naïve and NNRTI-experienced individuals. 19th EACS, 18–21 October 2023, Warsaw, Poland.. Oral Presentation PS 1.05.
https://eacs2023.abstractserver.com/program/#/details/presentations/546 (abstract)
https://live.allintheloop.net/Agenda/EACS/EACS2023/greenLiveStream/444748/2 (webcast with login)