Abstract:
BACKGROUND:Neuraminidase (NA) inhibitors (NAIs), including oseltamivir and zanamivir, play an important therapeutic role against influenza infections in immunocompromised patients. In such settings, however, NAI therapy may lead to the emergence of resistance involving mutations within the influenza surface genes. The aim of this study was to investigate the evolution of NA and haemagglutinin (HA) genes of influenza A(H1N1)pdm09 virus in an immunocompromised patient receiving oseltamivir then zanamivir therapies. METHODS:Nasopharyngeal swab (NPS) samples were collected between 27 January 2018 and 11 April 2018 from a haematopoietic stem cell transplant recipient. These include 10 samples collected either pre-therapy, during oseltamivir and zanamivir treatment as well as after therapy. The A(H1N1)pdm09 HA/NA genes were sequenced. The H275Y NA substitution was quantified by droplet digital RT-PCR assay. A(H1N1)pdm09 recombinant viruses containing HA mutations were tested by HA elution experiments to investigate in vitro binding properties. RESULTS:Oseltamivir rapidly induced the H275Y NA mutation which constituted 98.33% of the viral population after 15 days of oseltamivir treatment. The related HA gene contained S135A and P183S substitutions within the receptor-binding site. After a switch to zanamivir, 275H/Y and 119E/G/D mixed populations were detected. In the last samples, the double H275Y-E119G NA variant dominated with S135A and P183S HA substitutions. CONCLUSIONS:This report confirms that oseltamivir can rapidly induce the emergence of the H275Y substitution in A(H1N1)pdm09 viruses and subsequent switch to zanamivir can lead to additional substitutions at codon E119 resulting in multi-drug resistance. Such data additionally suggest a potential compensatory role for HA substitutions near the receptor binding site.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Abed Y,Schibler M,Checkmahomed L,Carbonneau J,Venable MC,Fage C,Giannotti F,Goncalves AR,Kaiser L,Boivin Gdoi
10.3851/IMP3344subject
Has Abstractpub_date
2019-01-01 00:00:00pages
581-587issue
8eissn
1359-6535issn
2040-2058journal_volume
24pub_type
杂志文章abstract::Zidovudine treatment of human immunodeficiency virus (HIV) infection induces drug-resistant viral strains harbouring specific amino acid substitutions in the reverse transcriptase (RT). To investigate whether this phenomenon could be observed in the case of human T lymphotropic virus type I (HTLV-I) infection, we anal...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to pregnant women alone or in combination with other antiretroviral drugs, greatly reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of these molecules is underestimated and wide-ranging evaluation of its biological and cl...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
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journal_title:Antiviral therapy
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doi:10.3851/IMP2777
更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
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doi:10.3851/IMP2951
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Antiviral therapy
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doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Mutations in the genome of HIV conferring drug resistance are a major reason for the failure of antiretroviral therapy, but they often compromise viral fitness. Protease (PR) cleavage site (CS) mutations could compensate for impaired replication capacity of drug-resistant viruses. PATIENTS AND METHODS:We an...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:2004-10-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract::Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data, but only limited clinical information on the effectiveness of licensed antiviral agents for the treatment of bacterial complications of ...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1730
更新日期:2011-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Hepatitis delta virus (HDV) infection therapy is unclear. This systematic analysis aimed to clarify the evidence on the efficacy of interferon (IFN)-α-based therapy in HDV. METHODS:We performed a systematic search on electronic databases including MEDLINE (1970 to January 2011), Web of Science, The Cochrane...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2306
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Clinical utilization of genotype resistance testing is evolving. We examined the extent to which HIV care providers requesting genotype resistance tests used the information appropriately and the impact of inappropriate utilization. METHODS:Data from a prospective cohort of HIV-infected patients (the HIV Ou...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3180
更新日期:2017-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:10.3851/IMP1780
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journal_title:Antiviral therapy
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3340
更新日期:2020-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2007-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 评论,杂志文章
doi:10.3851/IMP2498
更新日期:2012-01-01 00:00:00
abstract::The potential uses of serological tests that detect HCV core antigens in biological fluids are highlighted. The most common serological tests utilized to detect exposure to HCV rely on the detection of antibodies to HCV. However, these tests cannot distinguish between individuals who have resolved their infection and ...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2463
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND/AIMS:We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-alpha) and ribavirin combination therapy for patients with chronic hepatitis C and B virus (HCV/HBV) coinfection and to elucidate the interaction of these two viruses. METHODS:Forty-two chronic HCV/HBV-coinfected pat...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lam...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Little is known about the efficacy, safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis Cvirus (HCV) infection and histologically proven fully established cirrhosis. We aimed here to evaluate the safety of this regimen in such patients and to identify b...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2008-01-01 00:00:00
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pub_type: 杂志文章
doi:10.3851/IMP3373
更新日期:2020-11-19 00:00:00