Switch to BIC/TAF/FTC or DTG + TDF/FTC in virologically suppressed PWH: outcomes in real-world setting with and without tenofovir resistance

Abstract

Background: We evaluated whether switching to bictegravir/tenofovir alafenamide/emtrictabine (BIC/TAF/FTC) or dolutegravir (DTG)/tenofovir disoproxil fumarate (TDF)/FTC in PWH with virological success increased risks of virological failure (VF).

Methods: Analysis embedded in the French national Dat'AIDS cohort (NCT02898987) of all PWH followed after 1st January 2014, with no history of DTG and BIC exposure or resistance, and with a viral load < 50 copies/mL for more than twelve months. Switchers changed their antiretroviral regimen to BIC/TAF/FTC or DTG + TDF/FTC. VF defined as one value > 200 copies/mL. Marginal Structural Models compared VF in switchers and non-switchers, emulating a target trial. A multivariate Cox model assessed tenofovir resistance with VF in switchers only.

Results: 9827 PWH of whom 1393 (14.2%) switched to BIC/TAF/FTC or DTG + TDF/FTC. We observed 75 (5.4%) VF in switchers and 523 (6.2%) in non-switchers. After weighing, switching was associated with a non-significant risk of VF (HR of 1.29, 95% CI (0.97-1.7) (p=0.08). Presence of possible resistance and resistance to tenofovir (ANRS resistance algorithm) was not associated with VF (HR of 1.12, 95% CI (0.82-1.5), (p=0.47)) In switchers only, tenofovir resistance was not associated with VF (HR: 1.04, 95% CI (0.47-2.33)), nor was M184V or M184I mutations (HR: 0.98, 95% CI (0,5-2,1)).

Conclusions: in a real-world setting, switching to BIC/TAF/FTC or DTG + TDF/FTC in PWH with virological success was associated with a non-significant risk of VF, but M184V or M184I mutations and tenofovir resistance had no effect on VF. Most VF were blips or related to unmeasured adherence issues.

Keywords: bictegravir; dolutegravir; integrate inhibitors; switch; tenofovir resistance; thymidine analog mutations.