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).
Collins Iwuji, Laura Waters, Ana Milinkovic, Chloe Orkin, Julie Fox, Frank Post, Nicky Perry, Chloe Bruce, Natalie Dailey, Ye To, Stephen Bremner, Duncan Churchill, Anna Maria Geretti
{"title":"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).","authors":"Collins Iwuji, Laura Waters, Ana Milinkovic, Chloe Orkin, Julie Fox, Frank Post, Nicky Perry, Chloe Bruce, Natalie Dailey, Ye To, Stephen Bremner, Duncan Churchill, Anna Maria Geretti","doi":"10.1186/s12985-025-02648-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Historical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching.</p><p><strong>Registration: </strong>EudraCT no: 2018-004732-30.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"33"},"PeriodicalIF":4.0000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808997/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virology Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12985-025-02648-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies.
The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
