A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs

Hertogs, Kurt; Béthune, Marie‐Pierre de; Miller, Veronica; Ivens, Tania; Schel, Patricia; Cauwenberge, A Van; Eynde, Christel Van den; Gerwen, Veerle van; Azijn, Hilde; Houtte, Margriet Van; Peeters, Frank J C; Staszewski, Schlomo; Conant, Marcus A.; Bloor, Stuart; Kemp, Sharon D.; Larder, Brendan A.; Pauwels, Rudi

doi:10.1128/aac.42.2.269

Cited by 274 publications

(111 citation statements)

References 40 publications

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“…Of these, Virco's (Virco, Mechelen, Belgium) virco Ò TYPE HIV-1 (vT) and Antivirogram Ò (AVG), and Monogram Biosciences' (Monogram Biosciences, Inc., South San Francisco, CA) PhenoSenseÔ (PS) assays are used most widely. AVG and PS are conventional phenotypic assays measuring fold-changes in IC 50 (FC) in vitro, while vT provides calculated fold-changes in IC 50 from a viral genotype using the VirtualPhenotypeÔ-LM (VPT-LM) bioinformatics tool and a large database of viral isolates for which genotypic and phenotypic information is available and correlated [Hertogs et al, 1998;Petropoulos et al, 2000;Vermeiren et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

A comparison of HIV‐1 drug susceptibility as provided by conventional phenotyping and by a phenotype prediction tool based on viral genotype

Houtte¹,

Picchio²,

Borght³

et al. 2009

Journal of Medical Virology

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Concordance between the conventional HIV-1 phenotypic drug resistance assay, PhenoSense (PS), and vircoTYPE HIV-1 (vT), a drug resistance assay based on prediction of the phenotype, was investigated in a data set from the Stanford HIV Resistance database (hivdb). Depending on the drug, between 287 and 902 genotype-phenotype data pairs were available for comparisons. Test results (fold-change values) in the two assays were highly correlated, with an overall mean correlation coefficient of 0.90 using single PS measurements. This coefficient rose to 0.94 when the vT results were compared to the mean of repeat PS measurements. These results are comparable with the corresponding correlation coefficients of 0.87 and 0.95, calculated using single measurements, and the mean of repeat measurements, respectively, as obtained in the Antivirogram assay, the conventional HIV-1 phenotypic drug resistance test on which vT is based. The proportion of resistance calls resulting in a "major" discordance (fully susceptible or maximal response by one assay but fully resistant or minimal response by the other) ranged from 0% to 8.1% for drugs for which two clinical test cut-offs were available in both assays (didanosine, abacavir, tenofovir, saquinavir/r, fosamprenavir/r, and lopinavir/r), from 2.4% to 8.1% for the drugs for which two clinical test cut-offs were available in the vT assay and one clinical test cut-off in the PS assay (lamivudine, stavudine, indinavir/r, and atazanavir/r) and from 3.1% to 10.3% for drugs for which biological test cut-offs were used (zidovudine, nevirapine, delavirdine, efavirenz, indinavir, ritonavir, nelfinavir, saquinavir, and fosamprenavir). Our analyses suggest that these assays provide comparable resistance information, which will be of value to physicians who may be presented with either or both types of test report in their practice.

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Section: Introductionmentioning

confidence: 99%

A comparison of HIV‐1 drug susceptibility as provided by conventional phenotyping and by a phenotype prediction tool based on viral genotype

Houtte¹,

Picchio²,

Borght³

et al. 2009

Journal of Medical Virology

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“…Recent studies have focused on the development of recombinant virus assays, based on direct amplification of patient-derived sequences from plasma. Different systems in which recombinant viruses are generated by either homologous recombination [Hertogs et al, 1998] or direct cloning [Petropoulos et al, 2000;Klimkait, 2002] have demonstrated important advantages for large-scale applications. In addition to be fast and reproducible methods, shorter culture times minimize the outgrowth of minor variants in comparison with conventional phenotypic assays.…”

Section: Introductionmentioning

confidence: 99%

A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1

García-Pérez

Sánchez-Palomino

Pérez‐Olmeda

et al. 2006

Journal of Medical Virology

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The emergence of drug-resistant variants during antiretroviral therapy is a serious obstacle to sustained suppression of the human immunodeficiency virus type 1 (HIV-1). For that reason, resistance assays are essential to guide clinicians in the selection of optimal treatment regimens. Genotypic assays are less expensive and results are available faster than phenotypic assays. However, in heavily experienced patients with multiple treatment failures interpretation of complex mutation patterns remains difficult, and in these cases phenotypic assays are recommended. This report describes a novel recombinant virus assay where protease (PR) and reverse transcriptase (RT) sequences derived from the plasma isolated from patients are introduced into the back-bone of an HIV molecular clone that expresses Renilla luciferase protein in the place of nef gene. All drug resistance profiles analyzed correlate with previously reported data and showed high reproducibility. This assay, in addition to a fast (completed in 10 days), precise, reproducible and automated method, presents several advantages as compared to other phenotypic assays. The system described below allows the generation of recombinant viruses with multiples cycles of replication carrying a reporter gene in their genomes. These features increase the sensitivity of the test, an important aspect to be considered in the evaluation of less fit viral isolates. In conclusion, the assay permits the quantitation of the level of resistance of clinical HIV-1 isolates to PR and RT inhibitors.

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“…Genotypic changes were reported at codons associated with phenotypic resistance to NRTIs and NNRTIs. Phenotypic resistance assays to ddI, ddC, d4T, ZDV, 3TC and ABC were carried out by Virco NV, Belgium, using the recombinant virus assay [8]. Phenotype was expressed as fold resistance increase over wild-type (the ratio of wild-type to patients' variant IC 50 values).…”

Section: Baseline Genotypic and Phenotypic Analysesmentioning

confidence: 99%

Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48‐week data from a randomized, double‐blind trial

Katlama

Clotet²,

Plettenberg³

et al. 2001

HIV Medicine

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A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs

Cited by 274 publications

References 40 publications

A comparison of HIV‐1 drug susceptibility as provided by conventional phenotyping and by a phenotype prediction tool based on viral genotype

A comparison of HIV‐1 drug susceptibility as provided by conventional phenotyping and by a phenotype prediction tool based on viral genotype

A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1

Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48‐week data from a randomized, double‐blind trial

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