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Basic Characteristics of Mutations
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Mutation Site
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L90M |
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Mutation Site Sentence
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The remaining resistance mutation assays identified eight (4%) K103N, seven (3.5%) L90M, three (1.5%) Y181C, two (1.5%) M184V, one (0.5%) T215Y, and four (2%) T215F samples. Four samples (2% overall) had the following mutations to two drug classes: L90M+M184V, L90M+Y181C, Y181C+T215F, and L90M+M41L+K70R. |
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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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PR |
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Standardized Encoding Gene
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gag-pol
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Genotype/Subtype
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HIV-1 B |
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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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PIs |
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Location
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Canada;US |
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Literature Information
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PMID
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18666824
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Title
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Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy
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Author
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Johnson JA,Li JF,Wei X,Lipscomb J,Irlbeck D,Craig C,Smith A,Bennett DE,Monsour M,Sandstrom P,Lanier ER,Heneine W
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Journal
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PLoS medicine
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Journal Info
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2008 Jul 29;5(7):e158
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Abstract
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BACKGROUND: Transmitted HIV-1 drug resistance can compromise initial antiretroviral therapy (ART); therefore, its detection is important for patient management. The absence of drug-associated selection pressure in treatment-naive persons can cause drug-resistant viruses to decline to levels undetectable by conventional bulk sequencing (minority drug-resistant variants). We used sensitive and simple tests to investigate evidence of transmitted drug resistance in antiretroviral drug-naive persons and assess the clinical implications of minority drug-resistant variants. METHODS AND FINDINGS: We performed a cross-sectional analysis of transmitted HIV-1 drug resistance and a case-control study of the impact of minority drug resistance on treatment response. For the cross-sectional analysis, we examined viral RNA from newly diagnosed ART-naive persons in the US and Canada who had no detectable (wild type, n = 205) or one or more resistance-related mutations (n = 303) by conventional sequencing. Eight validated real-time PCR-based assays were used to test for minority drug resistance mutations (protease L90M and reverse transcriptase M41L, K70R, K103N, Y181C, M184V, and T215F/Y) above naturally occurring frequencies. The sensitive real-time PCR testing identified one to three minority drug resistance mutation(s) in 34/205 (17%) newly diagnosed persons who had wild-type virus by conventional genotyping; four (2%) individuals had mutations associated with resistance to two drug classes. Among 30/303 (10%) samples with bulk genotype resistance mutations we found at least one minority variant with a different drug resistance mutation. For the case-control study, we assessed the impact of three treatment-relevant drug resistance mutations at baseline from a separate group of 316 previously ART-naive persons with no evidence of drug resistance on bulk genotype testing who were placed on efavirenz-based regimens. We found that 7/95 (7%) persons who experienced virologic failure had minority drug resistance mutations at baseline; however, minority resistance was found in only 2/221 (0.9%) treatment successes (Fisher exact test, p = 0.0038). CONCLUSIONS: These data suggest that a considerable proportion of transmitted HIV-1 drug resistance is undetected by conventional genotyping and that minority mutations can have clinical consequences. With no treatment history to help guide therapies for drug-naive persons, the findings suggest an important role for sensitive baseline drug resistance testing.
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Sequence Data
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EU439613-EU439615
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