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Basic Characteristics of Mutations
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Mutation Site
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E138G |
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Mutation Site Sentence
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Several additional DRMs not on the SDRM list were analyzed including (1) the primarily tenofovir disoproxil fumarate (TDF)-selected DRMs A62V, K65N, and K70G/N/Q/S/T and (2) the primarily rilpivirine (RPV)-selected DRMs E138A/G/K/Q, of which E138A is polymorphic, occurring in 1%-4% of viruses from ART-naive individuals. |
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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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- |
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Treatment
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rilpivirine (RPV) |
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Location
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America |
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Literature Information
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PMID
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29846534
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Title
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Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population
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Author
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Rhee SY,Clutter D,Fessel WJ,Klein D,Slome S,Pinsky BA,Marcus JL,Hurley L,Silverberg MJ,Kosakovsky Pond SL,Shafer RW
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Journal
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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Journal Info
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2019 Jan 7;68(2):213-221
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Abstract
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BACKGROUND: There are few large studies of transmitted drug resistance (TDR) prevalence and the drug resistance mutations (DRMs) responsible for TDR in the United States. METHODS: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease sequences were obtained from 4253 antiretroviral therapy (ART)-naive individuals in a California clinic population from 2003 to 2016. Phylogenetic analyses were performed to study linkages between TDR strains and selection pressure on TDR-associated DRMs. RESULTS: From 2003 to 2016, there was a significant increase in overall (odds ratio [OR], 1.05 per year [95% confidence interval CI, 1.03-1.08]; P < .001) and nonnucleoside RT inhibitor (NNRTI)-associated TDR (OR, 1.11 per year [95% CI, 1.08-1.15]; P < .001). Between 2012 and 2016, TDR rates to any drug class ranged from 15.7% to 19.2%, and class-specific rates ranged from 10.0% to 12.8% for NNRTIs, 4.1% to 8.1% for nucleoside RT inhibitors (NRTIs), and 3.6% to 5.2% for protease inhibitors. The thymidine analogue mutations, M184V/I and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. Thirty-seven percent of TDR strains clustered with other TDR strains sharing the same DRMs. CONCLUSIONS: Although TDR has increased significantly in this large cohort, many TDR strains are unlikely to influence the activity of currently preferred first-line ART regimens. The high proportion of DRMs associated with infrequently used regimens combined with the clustering of TDR strains suggest that some TDR strains are being transmitted between ART-naive individuals.
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Sequence Data
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MG941022-MG944215
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