Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure
| Autor: | Fisher, Randall G, Smith, Davey M, Murrell, Ben, Slabbert, Ruhan, Kirby, Bronwyn M, Edson, Clair, Cotton, Mark F, Haubrich, Richard H, Kosakovsky Pond, Sergei L, Van Zyl, Gert U |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Genotype Anti-HIV Agents Clinical Sciences HIV Infections Microbial Sensitivity Tests Microbiology Mutation Rate Antiretroviral Therapy Highly Active Next generation sequencing Virology Drug Resistance Viral Humans Nevirapine Retrospective Studies Non-nucleoside reverse transcriptase inhibitor resistance Minor variant antiretroviral drug resistance mutations Infant Newborn virus diseases Computational Biology Infant High-Throughput Nucleotide Sequencing Viral Load Infectious Disease Transmission Vertical Prevention of mother to child transmission CD4 Lymphocyte Count Medical Microbiology Mutation HIV-1 RNA Viral Female HIV-1 drug resistance |
| Zdroj: | Fisher, Randall G; Smith, Davey M; Murrell, Ben; Slabbert, Ruhan; Kirby, Bronwyn M; Edson, Clair; et al.(2015). Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure.. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 62, 48-53. doi: 10.1016/j.jcv.2014.11.014. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/7s00s5qc |
| DOI: | 10.1016/j.jcv.2014.11.014. |
| Popis: | Next generation sequencing (NGS) allows the detection of minor variant HIV drug resistance mutations (DRMs). However data from new NGS platforms after Prevention-of-Mother-to-Child-Transmission (PMTCT) regimen failure are limited.To compare major and minor variant HIV DRMs with Illumina MiSeq and Life Technologies Ion Personal Genome Machine (PGM) in infants infected despite a PMTCT regimen.We conducted a cross-sectional study of NGS for detecting DRMs in infants infected despite a zidovudine (AZT) and Nevirapine (NVP) regimen, before initiation of combination antiretroviral therapy. Sequencing was performed on PCR products from plasma samples on PGM and MiSeq platforms. Bioinformatic analyses were undertaken using a codon-aware version of the Smith-Waterman mapping algorithm and a mixture multinomial error filtering statistical model.Of 15 infants, tested at a median age of 3.4 months after birth, 2 (13%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (K103N and Y181C) by bulk sequencing, whereas PGM detected 4 (26%) and MiSeq 5 (30%). NGS enabled the detection of additional minor variant DRMs in the infant with K103N. Coverage and instrument quality scores were higher with MiSeq, increasing the confidence of minor variant calls.NGS followed by bioinformatic analyses detected multiple minor variant DRMs in HIV-1 RT among infants where PMTCT failed. The high coverage of MiSeq and high read quality improved the confidence of identified DRMs and may make this platform ideal for minor variant detection. |
| Databáze: | OpenAIRE |
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