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Basic Characteristics of Mutations
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Mutation Site
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L210W |
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Mutation Site Sentence
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Among TDRMs with a potential impact on the NRTI employed, M184V/I was the most frequent (19 cases, 1.7%), followed by M41L (17 cases, 1.6%), T215F/Y (five cases, 0.5%), L74V (four cases, 0.4%), L210W (four cases, 0.4%), Y115F (three cases, 0.3%), K70R (three cases, 0.3%) and K65R (two cases, 0.2%). |
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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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NRTIs |
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Location
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Europe;Sub-Saharan Africa;South America;Middle East;South-east Asia |
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Literature Information
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PMID
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32964671
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Title
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Transmitted drug resistance to NRTIs and risk of virological failure in naive patients treated with integrase inhibitors
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Author
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Borghetti A,Ciccullo A,Lombardi F,Baldin G,Belmonti S,Prosperi M,Incardona F,Heger E,Borghi V,Sonnerborg A,Zazzi M,De Luca A,Di Giambenedetto S
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Journal
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HIV medicine
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Journal Info
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2021 Jan;22(1):22-27
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Abstract
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OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. METHODS: Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load >/= 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. RESULTS: From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. CONCLUSIONS: NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.
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Sequence Data
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-
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