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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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Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients |
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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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abacavir (ABC);lamivudine (LAM);dolutegravir (DTG) |
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Location
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Netherlands;France;Switzerland;Italy |
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Literature Information
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PMID
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31660328
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Title
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Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients
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Author
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Olearo F,Nguyen H,Bonnet F,Yerly S,Wandeler G,Stoeckle M,Cavassini M,Scherrer A,Costagiola D,Schmid P,Gunthard HF,Bernasconi E,Boeni J,D'arminio Monforte A,Zazzi M,Rossetti B,Neau D,Bellecave P,Rijnders B,Reiss P,Wit F,Kouyos R,Calmy A
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Journal
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Open forum infectious diseases
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Journal Info
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2019 Jul 12;6(10):ofz330
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Abstract
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OBJECTIVE: The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. METHOD: This is an observational study from 5 European HIV cohorts among treatment-experienced adults with =50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. RESULTS: We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154-441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively). CONCLUSIONS: In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
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Sequence Data
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-
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