Genotypic resistance testing in routine clinical care

Dunn, David; Coughlin, Kate; Cane, Patricia A.

doi:10.1097/coh.0b013e32834732e8

Cited by 29 publications

(16 citation statements)

References 52 publications

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“…A multitude of genotypic (sequencing-based) and phenotypic (cell-based) assays have been developed to identify and quantify HIV-1 drug resistance, and in the case of CCR5 receptor antagonists, to determine HIV-1 coreceptor tropism (8,34,35,89). Most of these HIV-1 drug resistance or tropism tests correspond to methods developed and used in research settings; however, a few selected assays are commercially available.…”

Section: Discussionmentioning

confidence: 99%

“…Particular emphasis has been made on the limited sensitivities of genotypic HIV-1 tropism assays to detect minor non-R5 variants (16,31), and to a lesser extent on the ability of genotypic HIV-1 drug resistance tests to detect minority drug-resistant variants (32)(33)(34). In the case of HIV-1 drug resistance, the vast amount of information accumulated during the last 2 decades by correlating mutations with phenotypic data has led to the almost exclusive use of genotypic antiretroviral testing based on population (Sanger) sequencing to manage patients infected with HIV-1 (2,35).…”

mentioning

confidence: 99%

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Sensitive Deep-Sequencing-Based HIV-1 Genotyping Assay To Simultaneously Determine Susceptibility to Protease, Reverse Transcriptase, Integrase, and Maturation Inhibitors, as Well as HIV-1 Coreceptor Tropism

Gibson

Meyer

Winner

et al. 2014

Antimicrob Agents Chemother

111

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Sensitive Deep-Sequencing-Based HIV-1 Genotyping Assay To Simultaneously Determine Susceptibility to Protease, Reverse Transcriptase, Integrase, and Maturation Inhibitors, as Well as HIV-1 Coreceptor Tropism

Gibson

Meyer

Winner

et al. 2014

Antimicrob Agents Chemother

111

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“…IV drug resistance genotyping is considered standard of care for patient management (1). This test has the clinical value of detection of antiretroviral (ARV) resistance and allows the selection of a new ARV regimen in patients who have experienced failure of their current ARV therapy regimen.…”

mentioning

confidence: 99%

Evaluation of a Benchtop HIV Ultradeep Pyrosequencing Drug Resistance Assay in the Clinical Laboratory

et al. 2013

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f Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in clinical practice. Ultradeep pyrosequencing has shown to be effective in detecting such mutations. The lack of a standardized commercially based assay limits the wide use of this method in clinical settings. 454 Life Sciences (Roche) is developing an HIV ultradeep pyrosequencing assay for their benchtop sequencer. We assessed the prototype plate in the clinical laboratory. Plasma samples genotyped by the standardized TruGene kit were retrospectively tested by this assay. Drug-treated subjects failing therapy and drug-naive patients were included. DRM analysis was based on the International AIDS Society USA DRM list and the Stanford algorithm. The prototype assay detected all of the DRMs detected by TruGene and additional 50 low-abundance DRMs. Several patients had lowabundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the drug that elicited these mutations. Additional patient harbored low-abundance V32I major protease inhibitor mutation, which under darunavir selection evolved later to be detected by TruGene. Stanford analysis suggested that some of the low-abundance DRMs were likely to affect the resistance burden in these subjects. The prototype assay performs at least as well as TruGene and has the advantage of detecting low-abundance drug resistance mutations undetected by TruGene. Its ease of use and lab-scale platform will likely facilitate its use in the clinical laboratory. The extent to which the detection of low-abundance DRMs will affect patient management is still unknown, but it is hoped that use of such an assay in clinical practice will help resolve this important question.

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“…Bioinformatics tools for therapy optimization based on genotypic resistance have also been developed [ 15 , 19 -21 ]. However, in their current state, they do not obviate the need for expert advice in the choice of salvage therapy [ 15 ].…”

Section: Human Immunodeficiency Virusmentioning

confidence: 97%

Genomic Applications in the Clinical Management of Infectious Diseases

Lefterova

Banaei

Pinsky

2014

Genomic Applications in Pathology

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Genotypic resistance testing in routine clinical care

Abstract: The technology and interpretation of genotypic resistance tests is in a phase of rapid development. It remains uncertain which of these developments will become part of routine clinical practice.

Cited by 29 publications

References 52 publications

Sensitive Deep-Sequencing-Based HIV-1 Genotyping Assay To Simultaneously Determine Susceptibility to Protease, Reverse Transcriptase, Integrase, and Maturation Inhibitors, as Well as HIV-1 Coreceptor Tropism

Sensitive Deep-Sequencing-Based HIV-1 Genotyping Assay To Simultaneously Determine Susceptibility to Protease, Reverse Transcriptase, Integrase, and Maturation Inhibitors, as Well as HIV-1 Coreceptor Tropism

Evaluation of a Benchtop HIV Ultradeep Pyrosequencing Drug Resistance Assay in the Clinical Laboratory

Genomic Applications in the Clinical Management of Infectious Diseases

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