scholarly journals Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting

2009 ◽  
Vol 64 (3) ◽  
pp. 616-624 ◽  
Author(s):  
Maurizio Zazzi ◽  
Mattia Prosperi ◽  
Ilaria Vicenti ◽  
Simona Di Giambenedetto ◽  
Annapaola Callegaro ◽  
...  
2018 ◽  
Author(s):  
Jasper C Ho ◽  
Garway T Ng ◽  
Mathias Renaud ◽  
Art FY Poon

AbstractGenotypic resistance interpretation systems for the prediction and interpretation of HIV-1 antiretroviral resistance are an important part of the clinical management of HIV-1 infection. Current interpretation systems are generally hosted on remote webservers that enable clinical laboratories to generate resistance predictions easily and quickly from patient HIV-1 sequences encoding the primary targets of modern antiretroviral therapy. However they also potentially compromise a health provider’s ethical, professional, and legal obligations to data security, patient information confidentiality, and data provenance. Furthermore, reliance on web-based algorithms makes the clinical management of HIV-1 dependent on a network connection. Here, we describe the development and validation of sierra-local, an open-source implementation of the Stanford HIVdb genotypic resistance interpretation system for local execution, which aims to resolve the ethical, legal, and infrastructure issues associated with remote computing. This package reproduces the HIV-1 resistance scoring by the web-based Stanford HIVdb algorithm with a high degree of concordance (99.997%) and a higher level of performance than current methods of accessing HIVdb programmatically.


2014 ◽  
Vol 17 (1) ◽  
pp. 19315 ◽  
Author(s):  
Abou Abdallah Malick Diouara ◽  
Halimatou Diop Ndiaye ◽  
Ibrehima Guindo ◽  
Nestor Bangoura ◽  
Mohamed Cissé ◽  
...  

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kevin D. McCormick ◽  
Kerri J. Penrose ◽  
Chanson J. Brumme ◽  
P. Richard Harrigan ◽  
Raquel V. Viana ◽  
...  

ABSTRACT Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC50) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 × 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.


2012 ◽  
Vol 15 (6(Suppl 4)) ◽  
Author(s):  
E Castro ◽  
P Recordon-Pinson ◽  
J Papuchon ◽  
B Vetter ◽  
C Shah ◽  
...  

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11505 ◽  
Author(s):  
Dineke Frentz ◽  
Charles A. B. Boucher ◽  
Matthias Assel ◽  
Andrea De Luca ◽  
Massimiliano Fabbiani ◽  
...  

Aids Reviews ◽  
2017 ◽  
Vol 19 (4) ◽  
Author(s):  
Valentina Svicher ◽  
Giulia Marchetti ◽  
Adrianna Ammassari ◽  
Francesca Ceccherini-Silberstein ◽  
Loredana Sarmati ◽  
...  

2021 ◽  
Vol 137 ◽  
pp. 104779
Author(s):  
Maria Kantzanou ◽  
Maria A. Karalexi ◽  
Anduela Zivinaki ◽  
Elena Riza ◽  
Helen Papachristou ◽  
...  

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