Virology journal · 2025
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).
СтатьяРандомизированное исследованиеКлиническое исследование IV фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Iwuji Collins, Waters Laura, Milinkovic Ana, Orkin Chloe, Fox Julie, Post Frank, Perry Nicky, Bruce Chloe, Dailey Natalie, To Ye, Bremner Stephen, Churchill Duncan, Geretti Anna Maria
Аннотация
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 increased HbA1c and weight. Virological suppression was maintained at week-48. There were six discontinuations; four on B/F/TAF were drug-related and the two on bPI were not drug-related.
CONCLUSIONS: Historical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching.
REGISTRATION: EudraCT no: 2018-004732-30.
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 increased HbA1c and weight. Virological suppression was maintained at week-48. There were six discontinuations; four on B/F/TAF were drug-related and the two on bPI were not drug-related.
CONCLUSIONS: Historical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching.
REGISTRATION: EudraCT no: 2018-004732-30.
Предметные рубрики MeSH
HumansMaleHIV InfectionsFemaleAdultHIV-1Middle AgedDrug Resistance, ViralTenofovirAnti-HIV AgentsEmtricitabineTreatment OutcomeViral LoadDrug SubstitutionPyridonesHeterocyclic Compounds, 4 or More RingsAdenineGenotypeAntiretroviral Therapy, Highly ActiveMutationPiperazinesAlanineHIV Protease InhibitorsAmidesHeterocyclic Compounds, 3-Ring