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Basic Characteristics of Mutations
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Mutation Site
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M184I |
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Mutation Site Sentence
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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. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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NRTI |
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Location
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England |
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Literature Information
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PMID
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39930490
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Title
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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)
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Author
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Iwuji C,Waters L,Milinkovic A,Orkin C,Fox J,Post F,Perry N,Bruce C,Dailey N,To Y,Bremner S,Churchill D,Geretti AM
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Journal
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Virology journal
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Journal Info
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2025 Feb 10;22(1):33
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Abstract
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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.
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Sequence Data
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-
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