Switching to bictegravir/emtricitabine/tenofovir alafenamide in people with HIV and prior resistance mutations. Data from the Italian ARCA cohort: the BIC-BARRIER study. B/F/TAF switch: mutations and outcomes

Objectives To estimate the prevalence of NRTI and integrase strand transfer inhibitor (INSTI), drug resistance mutations (DRMs) in antiretroviral therapy (ART)-experienced people with HIV-1 (PWH) switched to bictegravir/emtricitabine/tenofovir alafenamide fumarate (B/F/TAF) and among those with HIV-RNA ≤50 copies/mL to assess the association with risk of viral rebound (VR). Methods Data from the ARCA cohort were used to estimate resistance prevalence assuming a binomial distribution; 95% confidence intervals (CIs) were reported. Standard survival analysis with time-fixed covariate measured at B/F/TAF initiation was used to evaluate the association between detected resistance and risk of confirmed VR >50 copies/mL (2 consecutive values). Findings We included 1414 PWH (973—69%—in the VR analysis). Overall, 27% were female, median age was 53 years (IQR 44–59). Major NRTI-DRMs were detected in 25% (95% CI: 22.5, 27.1). Major INSTI-DRMs affecting bictegravir were rare (0.6%, 95% CI: 0.2, 1.4). The overall rate of VR by 36 months was 5.3% (95% CI: 3.7–6.9%), confirming that viral rebound on B/F/TAF is a rare event. After controlling for confounding, NRTI resistance was not associated with VR, whereas a history of INSTI virological failure (VF) and major INSTI-DRMs were associated with VR (aRH 2.68, 95% CI: 1.40, 5.12; and aRH 4.21, 95% CI: 1.18, 15.02, respectively). Conclusions In our cohort of PWH who were switched to B/F/TAF, NRTI-DRMs were common, but B/F/TAF remained effective in maintaining viral suppression despite their presence. However, previous failure to INSTI-based regimens and major INSTI-DRMs were risk factors for VR.