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Article ; Online: Quantification and Explanation of the Variability of First-Dose Amikacin Concentrations in Critically Ill Patients Admitted to the Emergency Department: A Population Pharmacokinetic Analysis.

De Winter, Sabrina / van Hest, Reinier / Dreesen, Erwin / Annaert, Pieter / Wauters, Joost / Meersseman, Wouter / Van den Eede, Nele / Desmet, Stefanie / Verelst, Sandra / Vanbrabant, Peter / Peetermans, Willy / Spriet, Isabel

European journal of drug metabolism and pharmacokinetics

2021 Volume 46, Issue 5, Page(s) 653–663

Abstract: Background: There may be a difference between the determinants of amikacin exposure in emergency department (ED) versus intensive care (ICU) patients, and the peak amikacin concentration varies widely between patients. Moreover, when the first dose of ... ...

Abstract	Background: There may be a difference between the determinants of amikacin exposure in emergency department (ED) versus intensive care (ICU) patients, and the peak amikacin concentration varies widely between patients. Moreover, when the first dose of antimicrobials is administered to septic patients admitted to the ED, fluid resuscitation and vasopressors have just been initiated. Nevertheless, population pharmacokinetic modelling data for amikacin in ED patients are unavailable. Objective: The aim of this study was to quantify the interindividual variability (IIV) in the pharmacokinetics of amikacin in patients admitted to the ED and to identify the patient characteristics that explain this IIV. Methods: Patients presenting at the ED with severe sepsis or septic shock were randomly assigned to receive amikacin 25 mg/kg or 15 mg/kg intravenously. Blood samples were collected at 1, 6 and 24 h after the onset of the first amikacin infusion. Data were analysed using nonlinear mixed-effects modelling. Results: A two-compartment population pharmacokinetic model was developed based on 279 amikacin concentrations from 97 patients. The IIV in clearance (CL) and central distribution volume (V Conclusion: The IIV of amikacin pharmacokinetics in ED patients is large. Higher doses may be considered in patients with low serum sodium levels, low total protein levels, or a high fluid balance. Trial registration: ClinicalTrials.gov ID: NCT02365272.
MeSH term(s)	Aged ; Aged, 80 and over ; Amikacin/administration & dosage ; Amikacin/pharmacokinetics ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/pharmacokinetics ; Critical Illness ; Dose-Response Relationship, Drug ; Emergency Service, Hospital ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Models, Biological ; Prospective Studies ; Sepsis/drug therapy ; Shock, Septic/drug therapy ; Tissue Distribution
Chemical Substances	Anti-Bacterial Agents ; Amikacin (84319SGC3C)
Language	English
Publishing date	2021-07-23
Publishing country	France
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	196729-0
ISSN	2107-0180 ; 0398-7639 ; 0378-7966
ISSN (online)	2107-0180
ISSN	0398-7639 ; 0378-7966
DOI	10.1007/s13318-021-00698-w
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Article: Neuroendocrine and Inflammatory Effects of Childhood Trauma Following Psychosocial and Inflammatory Stress in Women with Remitted Major Depressive Disorder.

Cassiers, Laura L M / Niemegeers, Peter / Fransen, Erik / Morrens, Manuel / De Boer, Peter / Van Nueten, Luc / Claes, Stephan / Sabbe, Bernard G C / Van Den Eede, Filip

Brain sciences

2019 Volume 9, Issue 12

Abstract: The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of ... ...

Abstract	The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of childhood trauma. In a single-blind randomized placebo-controlled crossover study, 21 women with remitted recurrent MDD and 18 healthy controls were exposed to psychosocial stress (Trier social stress test) or inflammatory stress (typhoid vaccine), or both, to investigate the effects of childhood trauma on the neuroendocrine and inflammatory responses. Childhood trauma was assessed using the Childhood Trauma Questionnaire and participants were dichotomized into a traumatized and non-traumatized group. Serum adrenocorticotropic hormone (ACTH), cortisol, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured at regular intervals after each intervention. The effects of trauma, time, and intervention on these parameters were modeled by fitting linear mixed models. Childhood trauma in itself did not have a main effect on the outcome measurements. However, an interactional effect of trauma with stressor type was found in the remitted MDD group: trauma was associated with higher cortisol levels only after adding immunological to psychosocial stress, and with lower TNF-α levels in response to vaccination. This suggests the existence of a vulnerable trauma-associated MDD endophenotype.
Language	English
Publishing date	2019-12-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci9120375
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Article ; Online: Age as a determinant of phosphate flame retardant exposure of the Australian population and identification of novel urinary PFR metabolites.

Van den Eede, Nele / Heffernan, Amy L / Aylward, Lesa L / Hobson, Peter / Neels, Hugo / Mueller, Jochen F / Covaci, Adrian

Environment international

2015 Volume 74, Page(s) 1–8

Abstract: The demand for alternative flame retardant materials such as phosphate flame retardants and plasticizers (PFRs) is increasing, although little is known of their possible effects on human health and development. To date, no information on the exposure of ... ...

Abstract	The demand for alternative flame retardant materials such as phosphate flame retardants and plasticizers (PFRs) is increasing, although little is known of their possible effects on human health and development. To date, no information on the exposure of children or general Australian population to PFRs is available. The objectives of this study were to characterize the average levels and age-related patterns of PFR metabolites in urine in the general Australian population and to identify novel hydroxylated PFR metabolites in urine. Surplus pathology urine samples from Queensland, Australia were stratified and pooled by age and sex (3224 individuals aged 0 to 75years into 95 pools) according to two different pooling strategies at two different time periods. Samples were analyzed by solid phase extraction and liquid chromatography-tandem mass spectrometry following enzymatic treatment. Nine PFR metabolites were measured in the Australian population, including the first report of a hydroxylated metabolite of TCIPP (BCIPHIPP). Diphenyl phosphate (DPHP), BCIPHIPP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were detected in >95% of samples. DPHP, a metabolite of aryl-PFRs, was found in several samples at levels which were one order of magnitude higher than previously reported (up to 730ng/mL). Weighted linear regression revealed a significant negative association between log-normalized BDCIPP and DPHP levels and age (p<0.001). Significantly greater levels of BDCIPP and DPHP were found in children's urine compared with adults, suggesting higher exposure to PFRs in young children. BCIPHIPP was identified for inclusion in future PFR biomonitoring studies.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Environmental Exposure ; Female ; Flame Retardants/metabolism ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Organophosphates/chemistry ; Organophosphates/urine ; Plasticizers/chemistry ; Plasticizers/metabolism ; Queensland ; Young Adult
Chemical Substances	Flame Retardants ; Organophosphates ; Plasticizers
Language	English
Publishing date	2015-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2014.09.005
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Article ; Online: A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing.

Petrillo, Mauro / Fabbri, Marco / Kagkli, Dafni Maria / Querci, Maddalena / Van den Eede, Guy / Alm, Erik / Aytan-Aktug, Derya / Capella-Gutierrez, Salvador / Carrillo, Catherine / Cestaro, Alessandro / Chan, Kok-Gan / Coque, Teresa / Endrullat, Christoph / Gut, Ivo / Hammer, Paul / Kay, Gemma L / Madec, Jean-Yves / Mather, Alison E / McHardy, Alice Carolyn /

Naas, Thierry / Paracchini, Valentina / Peter, Silke / Pightling, Arthur / Raffael, Barbara / Rossen, John / Ruppé, Etienne / Schlaberg, Robert / Vanneste, Kevin / Weber, Lukas M / Westh, Henrik / Angers-Loustau, Alexandre

F1000Research

2021 Volume 10, Page(s) 80

Abstract: Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain ... ...

Abstract	Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain "live" (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines' implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Benchmarking ; Computational Biology/methods ; Drug Resistance, Bacterial/genetics ; High-Throughput Nucleotide Sequencing/methods
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.39214.2
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Article ; Online: Differential Effects of Inflammatory and Psychosocial Stress on Mood, Hypothalamic-Pituitary-Adrenal Axis, and Inflammation in Remitted Depression.

Niemegeers, Peter / De Boer, Peter / Dumont, Glenn J H / Van Den Eede, Filip / Fransen, Erik / Claes, Stephan J / Morrens, Manuel / Sabbe, Bernard G C

Neuropsychobiology

2016 Volume 74, Issue 3, Page(s) 150–158

Abstract: Background/aims: Major depressive disorder (MDD) is highly recurrent. This may be due to increased stress sensitivity after remission. Both inflammatory and psychosocial stressors are implicated in the pathogenesis of MDD, but the additive or ... ...

Abstract	Background/aims: Major depressive disorder (MDD) is highly recurrent. This may be due to increased stress sensitivity after remission. Both inflammatory and psychosocial stressors are implicated in the pathogenesis of MDD, but the additive or differential effect is unclear. Methods: We conducted a single-blind placebo-controlled study to investigate the effects of inflammatory stress (i.e., typhoid vaccination), psychosocial stress (i.e., Trier Social Stress Test [TSST]), or a combination of both in women (25-45 years old) with (partially) remitted recurrent MDD (n = 21) and healthy female controls (n = 18). We evaluated the effect on mood measured by the Profile of Mood States, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity, and inflammatory system activation. The study was performed during 2 testing days, separated by a washout of 7-14 days. In a crossover design, subjects received one of the interventions on one day and placebo on the other. Results: A lowering of mood was seen in patients (β [95% CI] = -4.79 [-6.82 to -2.75], p < 0.001) only after vaccination, but not after the TSST or the combination; this effect was not observed in controls. Controls experienced a significantly different response on adrenocorticotropic hormone (ACTH) after vaccination, with a general rise in ACTH not observed in patients. In both groups, the TSST activated the HPA axis and suppressed the inflammatory parameters. Conclusions: There is a differential effect of inflammatory and psychosocial stress on mood and HPA axis activation in patients with remitted recurrent MDD. This may be an interesting treatment target in MDD.
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	442239-9
ISSN	1423-0224 ; 0302-282X
ISSN (online)	1423-0224
ISSN	0302-282X
DOI	10.1159/000466698
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Article ; Online: Urinary metabolites of organophosphate esters: Concentrations and age trends in Australian children.

He, Chang / Toms, Leisa-Maree L / Thai, Phong / Van den Eede, Nele / Wang, Xianyu / Li, Yan / Baduel, Christine / Harden, Fiona A / Heffernan, Amy L / Hobson, Peter / Covaci, Adrian / Mueller, Jochen F

Environment international

2017 Volume 111, Page(s) 124–130

Abstract: There is growing concern around the use of organophosphate esters (OPEs) due to their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs are used as flame retardants and plasticizers, and due to their extensive application in ... ...

Abstract	There is growing concern around the use of organophosphate esters (OPEs) due to their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs are used as flame retardants and plasticizers, and due to their extensive application in consumer products, are found globally in the indoor environment. Early life exposure to OPEs is an important risk factor for children's health, but poorly understood. To study age and sex trends of OPE exposures in infants and young children, we collected, pooled, and analysed urine samples from children aged 0-5years from Queensland, Australia for 9 parent OPEs and 11 metabolites. Individual urine samples (n=400) were stratified by age and sex, and combined into 20 pools. Three individual breast milk samples were also analysed to provide a preliminary estimate on the contribution of breast milk to the intake of OPEs. Bis(1-chloroisopropyl) phosphate (BCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), bis(1,3-dichloroisopropyl) phosphate (BDCIPP), dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3OH-TBOEP), and bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were detected in all urine samples, followed by bis(methylphenyl) phosphate (80%), and bis(2-ethylhexyl) phosphate (BEHP, 20%), and bis(2-chloroethyl) phosphate (BCEP, 15%). Concentrations of tris(2-chloroethyl) phosphate (TCEP), BCEP, tris(2-ethylhexyl) phosphate (TEHP), and DBP decreased with age, while bis(methylphenyl) phosphate (BMPP) increased with age. Significantly higher concentrations of DPHP (p=0.039), and significantly lower concentrations of TEHP (p=0.006) were found in female samples compared to males. The estimated daily intakes (EDIs) via breastfeeding, were 4.6, 26 and 76ng/kg/day for TCEP, TBP and TEHP, respectively, and were higher than that via air and dust, suggesting higher exposure through consumption of breast milk.
MeSH term(s)	Breast Feeding ; Child Health ; Child, Preschool ; Dust/analysis ; Environmental Monitoring/statistics & numerical data ; Esters/analysis ; Esters/urine ; Female ; Flame Retardants/analysis ; Humans ; Infant ; Infant, Newborn ; Male ; Milk, Human/chemistry ; Organophosphates/analysis ; Organophosphates/urine ; Plasticizers/analysis ; Queensland
Chemical Substances	Dust ; Esters ; Flame Retardants ; Organophosphates ; Plasticizers
Language	English
Publishing date	2017-11-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2017.11.019
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Article: Age as a determinant of phosphate flame retardant exposure of the Australian population and identification of novel urinary PFR metabolites

Van den Eede, Nele / Adrian Covaci / Amy L. Heffernan / Hugo Neels / Jochen F. Mueller / Lesa L. Aylward / Peter Hobson

Environment international. 2015 Jan., v. 74

2015

Abstract	The demand for alternative flame retardant materials such as phosphate flame retardants and plasticizers (PFRs) is increasing, although little is known of their possible effects on human health and development. To date, no information on the exposure of children or general Australian population to PFRs is available. The objectives of this study were to characterize the average levels and age-related patterns of PFR metabolites in urine in the general Australian population and to identify novel hydroxylated PFR metabolites in urine. Surplus pathology urine samples from Queensland, Australia were stratified and pooled by age and sex (3224 individuals aged 0 to 75years into 95 pools) according to two different pooling strategies at two different time periods. Samples were analyzed by solid phase extraction and liquid chromatographyâtandem mass spectrometry following enzymatic treatment. Nine PFR metabolites were measured in the Australian population, including the first report of a hydroxylated metabolite of TCIPP (BCIPHIPP). Diphenyl phosphate (DPHP), BCIPHIPP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were detected in >95% of samples. DPHP, a metabolite of aryl-PFRs, was found in several samples at levels which were one order of magnitude higher than previously reported (up to 730ng/mL). Weighted linear regression revealed a significant negative association between log-normalized BDCIPP and DPHP levels and age (p<0.001). Significantly greater levels of BDCIPP and DPHP were found in children's urine compared with adults, suggesting higher exposure to PFRs in young children. BCIPHIPP was identified for inclusion in future PFR biomonitoring studies.
Keywords	adults ; biphenyl ; children ; enzymatic treatment ; flame retardants ; human health ; liquid chromatography ; metabolites ; phosphates ; plasticizers ; regression analysis ; solid phase extraction ; tandem mass spectrometry ; urine ; Queensland
Language	English
Dates of publication	2015-01
Size	p. 1-8.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2014.09.005
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Article ; Online: Development, Evaluation, and Integration of a Quantitative Reverse-Transcription Polymerase Chain Reaction Diagnostic Test for Ebola Virus on a Molecular Diagnostics Platform.

Cnops, Lieselotte / Van den Eede, Peter / Pettitt, James / Heyndrickx, Leo / De Smet, Birgit / Coppens, Sandra / Andries, Ilse / Pattery, Theresa / Van Hove, Luc / Meersseman, Geert / Van Den Herrewegen, Sari / Vergauwe, Nicolas / Thijs, Rein / Jahrling, Peter B / Nauwelaers, David / Ariën, Kevin K

The Journal of infectious diseases

2016 Volume 214, Issue suppl 3, Page(s) S192–S202

Abstract: Background: The 2013-2016 Ebola epidemic in West Africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. We describe the development and evaluation of the Idylla™ prototype Ebola virus test, a fully ... ...

Abstract	Background: The 2013-2016 Ebola epidemic in West Africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. We describe the development and evaluation of the Idylla™ prototype Ebola virus test, a fully automated sample-to-result molecular diagnostic test for rapid detection of Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). Methods: The Idylla™ prototype Ebola virus test can simultaneously detect EBOV and SUDV in 200 µL of whole blood. The sample is directly added to a disposable cartridge containing all reagents for sample preparation, RNA extraction, and amplification by reverse-transcription polymerase chain reaction analysis. The performance was evaluated with a variety of sample types, including synthetic constructs and whole blood samples from healthy volunteers spiked with viral RNA, inactivated virus, and infectious virus. Results: The 95% limits of detection for EBOV and SUDV were 465 plaque-forming units (PFU)/mL (1010 copies/mL) and 324 PFU/mL (8204 copies/mL), respectively. In silico and in vitro analyses demonstrated 100% correct reactivity for EBOV and SUDV and no cross-reactivity with relevant pathogens. The diagnostic sensitivity was 97.4% (for EBOV) and 91.7% (for SUDV), the specificity was 100%, and the diagnostic accuracy was 95.9%. Conclusions: The Idylla™ prototype Ebola virus test is a fast, safe, easy-to-use, and near-patient test that meets the performance criteria to detect EBOV in patients with suspected Ebola.
MeSH term(s)	Africa, Western/epidemiology ; Disease Outbreaks ; Ebolavirus/genetics ; Ebolavirus/isolation & purification ; Hemorrhagic Fever, Ebola/diagnosis ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/virology ; Humans ; Molecular Diagnostic Techniques/instrumentation ; Molecular Diagnostic Techniques/methods ; RNA, Viral/analysis ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction/instrumentation ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Sensitivity and Specificity
Chemical Substances	RNA, Viral
Language	English
Publishing date	2016-10-15
Publishing country	United States
Document type	Evaluation Studies ; Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiw150
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Article ; Online: A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing [version 2; peer review

Alison E. Mather / Alice Carolyn McHardy / Ivo Gut / Gemma L. Kay / Kevin Vanneste / Arthur Pightling / John Rossen / Thierry Naas / Silke Peter / Henrik Westh / Alexandre Angers-Loustau / Etienne Ruppé / Robert Schlaberg / Marco Fabbri / Alessandro Cestaro / Maddalena Querci / Barbara Raffael / Mauro Petrillo / Paul Hammer /

Lukas M. Weber / Jean-Yves Madec / Valentina Paracchini / Guy Van den Eede / Erik Alm / Derya Aytan-Aktug / Dafni Maria Kagkli / Teresa Coque / Kok-Gan Chan / Christoph Endrullat / Salvador Capella-Gutierrez / Catherine Carrillo

F1000Research, Vol

1 approved, 2 approved with reservations]

2022 Volume 10

Abstract	Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain “live” (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines’ implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.
Keywords	Antimicrobial resistance ; bioinformatics ; next-generation sequencing ; benchmarking ; eng ; Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.

Jiamsakul, Awachana / Chaiwarith, Romanee / Durier, Nicolas / Sirivichayakul, Sunee / Kiertiburanakul, Sasisopin / Van Den Eede, Peter / Ditangco, Rossana / Kamarulzaman, Adeeba / Li, Patrick C K / Ratanasuwan, Winai / Sirisanthana, Thira

Journal of medical virology

2016 Volume 88, Issue 2, Page(s) 234–243

Abstract: HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among ... ...

Abstract	HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01_AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoType(TM) HIV-1 and Antivirogram®, respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01_AE strains were highly robust in comparison with the gold-standard PT.
MeSH term(s)	Anti-HIV Agents/pharmacology ; Asia ; Drug Resistance, Viral ; Genotype ; Genotyping Techniques/methods ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/genetics ; HIV-1/isolation & purification ; Humans ; Microbial Sensitivity Tests/methods ; Phenotype
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.24320
Database	MEDical Literature Analysis and Retrieval System OnLINE

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