Pironti, Alejandro, Walter, Hauke, Pfeifer, Nico ORCID: 0000-0002-4647-8566, Knops, Elena, Luebke, Nadine, Buech, Joachim, Di Giambenedetto, Simona, Kaiser, Rolf and Lengauer, Thomas (2017). Determination of Phenotypic Resistance Cutoffs From Routine Clinical Data. JAIDS, 74 (5). S. E129 - 9. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1077-9450

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Abstract

Background: HIV-1 drug resistance can be measured with phenotypic drug-resistance tests. However, the output of these tests, the resistance factor (RF), requires interpretation with respect to the in vivo activity of the tested variant. Specifically, the dynamic range of the RF for each drug has to be divided into a suitable number of clinically meaningful intervals. Methods: We calculated a susceptible-to-intermediate and an intermediate-to-resistant cutoff per drug for RFs predicted by (geno2pheno)[resistance]. Probability densities for therapeutic success and failure were estimated from 10,444 treatment episodes. The density estimation procedure corrects for the activity of the backbone drug compounds and for therapy failure without drug resistance. For estimating the probability of therapeutic success given an RF, we fit a sigmoid function. The cutoffs are given by the roots of the third derivative of the sigmoid function. Results: For performance assessment, we used geno2pheno[resistance] RF predictions and the cutoffs for predicting therapeutic success in 2 independent sets of therapy episodes. HIVdb was used for performance comparison. On one test set (n = 807), our cutoffs and HIVdb performed equally well receiver operating characteristic curve [(ROC)area under the curve (AUC): 0.68]. On the other test set (n = 917), our cutoffs (ROC-AUC: 0.63) and HIVdb (ROC-AUC: 0.65) performed comparatively well. Conclusions: Our method can be used for calculating clinically relevant cutoffs for (predicted) RFs. The method corrects for the activity of the backbone drug compounds and for therapy failure without drug resistance. Our method's performance is comparable with that of HIVdb. RF cutoffs for the latest version of (geno2pheno)[resistance] have been estimated with this method.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pironti, AlejandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, HaukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, NicoUNSPECIFIEDorcid.org/0000-0002-4647-8566UNSPECIFIED
Knops, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luebke, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buech, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Giambenedetto, SimonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lengauer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-233872
DOI: 10.1097/QAI.0000000000001198
Journal or Publication Title: JAIDS
Volume: 74
Number: 5
Page Range: S. E129 - 9
Date: 2017
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1077-9450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; DRUG-RESISTANCE; EXPERIENCED PATIENTS; ANTIVIRAL ACTIVITY; HIV-1 INFECTION; PHARMACOKINETIC PROPERTIES; ANTIRETROVIRAL TREATMENT; VIROLOGICAL RESPONSE; THERAPEUTIC-EFFICACYMultiple languages
Immunology; Infectious DiseasesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23387

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