Outcomes of switching from protease inhibitor-based antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed adults with nucleos(t)ide analogue resistance– a phase IV randomised, open-label study (PIBIK study)

作者：Collins Iwuji, Laura Waters, Ana Milinkovic, Chloe Orkin, Julie Fox, Frank A. Post, Nicky Perry, Chloe Bruce, Natalie Dailey Garnes, Ye To, Stephen Bremner, Duncan Churchill, Anna María Geretti · 发表于：Virology Journal · 年份：2025 · DOI：10.1186/s12985-025-02648-3 · 被引用次数：2 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV-related health complications and treatments

BACKGROUND: There are limited data on how historical nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs) other than M184V/I, affect the activity of B/F/TAF. We evaluated the outcomes of switching virologically suppressed (HIV-1 RNA < 50 copies/mL) individuals harbouring major RAMs from boosted protease inhibitor (bPI)-based therapy to B/F/TAF. METHODS: Participants had various historical genotypic patterns including M184V/I, ≤2 thymidine analogue mutations (TAMs), and other NRTI RAMs (NAMs), and no integrase resistance. Baseline RAMs were explored by retrospective sequencing of cellular HIV-1 DNA. Participants were randomised (1:1) to switching to B/F/TAF either immediately or after 24 weeks. The primary outcome was the proportion of participants maintaining virological suppression (pure virologic response) at week-24; secondary outcomes were proportion of participants with virological suppression at week-48, pre-specified safety measures, and treatment-emergent resistance. RESULTS: Historically, 21/72 (29.2%) participants had M184V/I, 5 (6.9%) M184V/I + 1 NAM, 31 (43.1%) 1 TAM ± M184V/I ± 1 NAM, and 15 (20.8%) 2 TAMs ± M184V/I ± 1 NAM. At week-24, proportions maintaining virological suppression were 33/33 (100%) on B/F/TAF vs. 38/39 (97.4%) on bPI (difference 2.6%; 95% CI -2.4%, 7.5%). Drug-related adverse events (AEs) were reported in 10/33 (30.3%) vs. 1/39 (2.6%), respectively. The immediate switch arm had improved lipid parameters but ...