scholarly journals Characterization of Novel HIV Drug Resistance Mutations Using Clustering, Multidimensional Scaling and SVM-Based Feature Ranking

Author(s):  
Tobias Sing ◽  
Valentina Svicher ◽  
Niko Beerenwinkel ◽  
Francesca Ceccherini-Silberstein ◽  
Martin Däumer ◽  
...  
Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 264
Author(s):  
Miaomiao Li ◽  
Shujia Liang ◽  
Chao Zhou ◽  
Min Chen ◽  
Shu Liang ◽  
...  

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.


2012 ◽  
Vol 84 (5) ◽  
pp. 721-727 ◽  
Author(s):  
Laura Ceccarelli ◽  
Romina Salpini ◽  
Sylvie Moudourou ◽  
Valeria Cento ◽  
Maria M. Santoro ◽  
...  

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10952 ◽  
Author(s):  
Max Lataillade ◽  
Jennifer Chiarella ◽  
Rong Yang ◽  
Steven Schnittman ◽  
Victoria Wirtz ◽  
...  

2005 ◽  
Vol 191 (3) ◽  
pp. 339-347 ◽  
Author(s):  
P. Richard Harrigan ◽  
Robert S. Hogg ◽  
Winnie W. Y. Dong ◽  
Benita Yip ◽  
Brian Wynhoven ◽  
...  

2008 ◽  
Vol 24 (9) ◽  
pp. 1133-1138 ◽  
Author(s):  
Maria Mercedes Santoro ◽  
Massimo Ciccozzi ◽  
Claudia Alteri ◽  
Stefania Montieri ◽  
Ivailo Alexiev ◽  
...  

2015 ◽  
Vol 20 (3) ◽  
pp. 253-259 ◽  
Author(s):  
Jean d’Amour Ndahimana ◽  
David J Riedel ◽  
Ribakare Muhayimpundu ◽  
Sabin Nsanzimana ◽  
Gad Niyibizi ◽  
...  

2017 ◽  
Author(s):  
Claudia Gonzalez ◽  
Jessica Gondola ◽  
Alma Y Ortiz ◽  
Juan M Castillo ◽  
Juan M Pascale ◽  
...  

ABSTRACTDetermination of HIV drug resistance (HIVDR) is becoming an integral baseline HIV evaluation for newly infected subjects, as the level of pre-treatment resistance is increasing worldwide. Until now, the gold standard for monitoring ART mutations is the Sanger sequencing method, however, next-generation sequencing technologies (NGS) because high-throughput capability, are gaining attention as a method for detection of HIVDR. In the present work, we evaluated the use of the Oxford Nanopore Technologies (ONT) MinION as an alternative method for detection of drug resistance mutations in pre-treatment HIV positive subjects.We evaluate 36 samples taken during November 2016 from treatment naïve subjects with age greater than 18 years old, who went to the lab for their first HIV monitoring. To evaluate the agreement between Sanger and MinION generated sequences, we aligned the sequences (∼1200bp) with muscle v. 3.8.31. Then we counted the differences and calculated the p-distance of the obtained sequences, comparing paired sequences and grouping Sanger and MinION obtained sequences. The percentage of similarity among each sequence was also evaluated.All samples were submitted to the Standford University HIV drug resistance database (HIVdb version 8.4). Then we compared the resistance predictions obtained from the sequences generated by Sanger and MinION methods.Results: The median of available pores was 1314 for the first run, 1215 for the second run, and 536 for the third run. After 3 hours with SQK-NSK007 a total of 18803 2D reads were base-called and in 16577 reads (88%) a barcode was detected.Comparing the nucleotide differences of each sample, we observed that 23 (74%) samples had identical sequence, for the other samples the percentage of identity among each analyzed sequence was greater than 95%. A good positive predictive value (100%) in the estimation of drug resistance mutations in the groups of protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs).We present an approach for the analysis of HIV reads generated with MinION ONT, further studies are guaranteed before the application of this methodology in clinical settings to assess its suitability for HIVDR testing.


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