Virological failure and resistance emergence during treatment with bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir/lamivudine in people living with HIV without prior resistance mutations: a real-world study.

OBJECTIVES

To evaluate, in a large real-world cohort of people living with HIV (PLWH) treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) or dolutegravir/lamivudine, rates of virological failure (VF) and resistance emergence.

METHODS

All PLWH receiving BIC/FTC/TAF or dolutegravir/lamivudine without prior NRTI or integrase strand transfer inhibitor (InSTI) resistance-associated mutations (RAMs) and with at least 6 month follow-up between January 2018 and January 2025 were included in this retrospective single-centre study. Demographic, therapeutic and immunovirological data were collected from electronic medical records. VF was defined as confirmed HIV RNA >50 copies/mL or a single HIV RNA >200 copies/mL followed by modification of treatment. Blip was defined as a single HIV RNA between 50 and 200 copies/mL. These thresholds were applied after >6 months of first-line therapy (FLT), or at any timepoint in virological suppression maintenance therapy (MT). Plasma HIV genotyping by Sanger sequencing was performed at the clinician's request, and resistance was interpreted using the ANRS algorithm V35.

RESULTS

A total of 1059 PLWH were included: 594 receiving BIC/FTC/TAF (141 FLT and 453 MT) and 465 receiving dolutegravir/lamivudine (23 FLT and 442 MT). VF occurred in 79/1059 PLWH (7.5% overall; 9.8% in the BIC/FTC/TAF group and 4.5% in the dolutegravir/lamivudine group) and blips in 96/1059 PLWH (9.0% overall; 9.9% and 5.8%, respectively, groupwise). Resistance emergence was documented in nine cases (0.9%), four for BIC/FTC/TAF (InSTI-RAM in 1/4) and five for dolutegravir/lamivudine (InSTI-RAM in 3/5).

CONCLUSIONS

In this real-world cohort, InSTI resistance emergence in PLWH failing BIC/FTC/TAF or dolutegravir/lamivudine was rare at 0.17% and 0.65%, respectively, supporting the robustness of these InSTI-based regimens.