Resistance to second-generation integrase inhibitors in people with HIV following treatment failure on dolutegravir-...

Resistance-associated mutations (RAMs) to second-generation integrase strand-transfer inhibitors (INSTIs) have been increasingly observed among people with HIV (PWH) who experienced virological failure on dolutegravir-based ART. However, data on dolutegravir resistance in the Asia-Pacific region remain limited, and data on RAMs during virological failure while receiving bictegravir-based ART are even more scarce.

In this multicentre, retrospective study in Taiwan, PWH with treatment failure on second-generation INSTI-based ART and successful amplification of the integrase gene were included. Data collected included HIV-1 subtypes, plasma viral loads (PVLs), CD4 counts and clinical characteristics. RAMs were identified using the 2025 IAS-USA mutation list and interpreted using the Stanford HIVdb algorithm.

From 2016 to 2022, 73 and 127 PWH experienced treatment failure on bictegravir- and dolutegravir-based ART, respectively, and had successful genotypic resistance testing. Median PVL at failure was 4.7 log10 copies/mL, and median CD4 count was 225 cells/mm3, with no significant between-group differences. RAMs to second-generation INSTIs were detected in 5.5% (4/73) of bictegravir- and 4.8% (6/127) of dolutegravir-treated individuals (P = 0.33). Common RAMs included Q148H/K/R (3.5%), G140A/C/R/S (3.0%) and R263K (1.5%), with comparable distributions between the two groups. Among eight PWH retained in care, four achieved viral suppression after switching to salvage ART, and four with continuation of INSTI-based ART.

Although RAMs to second-generation INSTIs may be detected during treatment failure, the overall prevalence remains low for both dolutegravir- and bictegravir-based ART. Viral resuppression can be achieved through salvage therapy or continued use of second-generation INSTI-based regimens.