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Basic Characteristics of Mutations
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Mutation Site
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G190S |
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Mutation Site Sentence
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Table 1. NNRTI resistance detected by single-genome sequencing. |
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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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Acquired Immunodeficiency Syndrome
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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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NNRTIs |
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Location
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- |
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Literature Information
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PMID
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20102272
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Title
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Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients
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Author
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Halvas EK,Wiegand A,Boltz VF,Kearney M,Nissley D,Wantman M,Hammer SM,Palmer S,Vaida F,Coffin JM,Mellors JW
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Journal
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The Journal of infectious diseases
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Journal Info
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2010 Mar;201(5):672-80
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Abstract
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BACKGROUND: The contribution of low frequency drug-resistant human immunodeficiency virus type 1 (HIV-1) variants to failure of antiretroviral therapy is not well defined in treatment-experienced patients. We sought to detect minor nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistant variants at the initiation of multidrug efavirenz-containing therapy in both NNRTI-naive and NNRTI-experienced patients and to determine their association with virologic response. METHODS: Plasma samples at entry and at time of virologic failure from patients enrolled in the AIDS Clinical Trials Group study 398 were analyzed by standard genotype, single-genome sequencing and allele-specific polymerase chain reaction (K103N and Y181C) to detect and quantify minor NNRTI-resistant variants. RESULTS: Minor populations of NNRTI-resistant variants that were missed by standard genotype were detected more often at study entry in NNRTI-experienced patients than NNRTI-naive patients by both single-genome sequencing (8 of 12 vs 3 of 15; P = .022) and allele-specific polymerase chain reaction (11% Y181C, 5 of 22 vs 3 of 72, respectively; P = .016). K103N variants at frequencies 11% were associated with inferior HIV-1 RNA response to efavirenz-containing therapy between entry and week 24 (change in HIV-1 RNA level, +0.5 vs -1.1 log(10) copies/mL; P < .001). CONCLUSIONS: Minor NNRTI-resistant variants were more prevalent in NNRTI-experienced patients and were associated with reduced virologic response to efavirenz-containing multidrug regimens.
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Sequence Data
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-
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