Abstract:
:HIV drug resistance remains one of the most important influences on long-term therapeutic prospects. Resistance and therapeutic failure arises out of the selection and preservation of randomly generated genomic mutations that confer a replicative advantage in the presence of one or more antiretrovirals. The primary correlate to the time to emergence of a drug-resistant HIV variant is the extent of residual replication under selecting drug pressure, emphasizing the importance of full virological suppression to long-term therapy. Further contributions to the time to emergence are the degree of selective pressure exerted by a given drug, whereby greater potency forces earlier selection of mutant strains in balance with the extent of residual replication, and the degree of reduced drug susceptibility afforded by a particular mutation. Once evolved, drug-resistant strains can persist indefinitely as minority viral populations or archived genomes in latently infected CD4 cells, despite long-term withdrawal of the selecting drugs, to reemerge rapidly on rechallenge with those or any cross-resistant drug. Variable adherence to medication in the routine clinical setting has given rise to resistance mutations being observed in some 50-60% of those with detectable viral loads on therapy in countries where antiretroviral therapy has been widely available. Nucleoside reverse transcriptase inhibitor-associated mutations form the majority of these, and the long and almost universal use of zidovudine and stavudine has led to mutations selected by these drugs being the most common observed, along with the primary lamivudine resistance mutation M184V. Transmission of drug-resistant HIV in cases of new infection has also been widely studied, and although the extent is considerably lower than that in the treated population (typically 4-10% outside certain geographic areas), early data suggest that it is rising over time as the infected source population becomes more therapy-experienced. Once again, mutations from zidovudine or, to a lesser extent, stavudine exposure form the majority of mutations observed in cases of primary transmission. These data are a cause for concern, and imply that, as things stand, the use of a drug resistance test may become as important to the design of an effective first-line highly active antiretroviral therapy regimen as they have become for selecting new drugs on therapeutic failure.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Pillay Dsubject
Has Abstractpub_date
2001-01-01 00:00:00pages
15-24eissn
1359-6535issn
2040-2058journal_volume
6 Suppl 3pub_type
杂志文章,评审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
abstract:BACKGROUND:With the advent of the protease inhibitors boceprevir and telaprevir a novel therapy approach for HCV genotype 1 infected subjects has become standard of care. Quantification of HCV viral load (VL) represents an important predictor of treatment response. METHODS:Two different real-time PCR platforms, the CO...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2723
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testin...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2780
更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3156
更新日期:2017-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2009-01-01 00:00:00
abstract::We report the first two paediatric cases of sofosbuvir treatment during high-intensity myeloablative conditioning and engraftment phases of haematopoietic stem cell transplantation. These reports highlight the safety of sofosbuvir during all phases of transplantation and the lack of interaction between sofosbuvir and ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3332
更新日期:2019-01-01 00:00:00
abstract::With the advent of the human immunodeficiency virus (HIV) protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug interactions with antiretroviral agents is becoming increasingly recognized. Every clinician involved in the care of HIV-infected persons should have a broa...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 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
doi:10.3851/IMP1931
更新日期:2011-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2743
更新日期:2014-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:10.3851/IMP2737
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting. METHODS:One-hundred and thirty HIV-1-infected adults with self-report...
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
abstract::Chronic hepatitis C affects approximately 170 million people worldwide and is one of the leading causes of liver-related morbidity and mortality. Until 2011, the only therapeutic option was combination therapy of pegylated interferon and ribavirin, with efficacy rates around 50% and plenty of side effects. In the past...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2425
更新日期:2012-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3372
更新日期:2020-10-22 00:00:00
abstract:BACKGROUND:No data are available on the clinical presentation and virological pattern in the case of failure of interferon (IFN)-free regimens in patients with genotype-3h. In this paper authors identified the virological and clinical characteristics of patients with genotype-3h treated with suboptimal or not indicated...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3228
更新日期:2018-01-01 00:00:00
abstract::Cytomegalovirus (CMV) remains a leading cause of morbidity after solid organ transplantation. The efficiency of antivirals for the treatment of CMV infections may be hampered because of the emergence of CMV resistance to antivirals. The development of CMV multidrug resistance, which remains uncommon but does occur, co...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2818
更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2897
更新日期:2014-01-01 00:00:00
abstract::HBV is a hepatotropic and non-cytopathic virus that causes more than one million deaths annually from liver cirrhosis and hepatocellular carcinoma. As the virus itself is non-cytopathic, it is widely accepted that both viral control and liver pathology are mediated by the host immune system. Until recently, the focus ...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1620
更新日期:2010-01-01 00:00:00
abstract::Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from H...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in c...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1796
更新日期:2011-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:ITX 5061 is a highly potent small molecule inhibitor of scavenger receptor-B1, an integral transmembrane protein that is found in liver cells and is actively involved in the transport of HCV into hepatocytes. Currently, ITX 5061 is being investigated in monoinfected hepatitis C patients in a proof-of-concept...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2354
更新日期:2013-01-01 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:2003-10-01 00:00:00
abstract:BACKGROUND:New drugs are needed to combat HBV infection. We investigated the anti-HBV activity of the deoxycytidine analogue FNC, which has anticancer activity and has been found to inhibit HCV replication. METHODS:In this study, a human hepatoma HepG2.2.15 cell culture system and duck HBV (DHBV) infection model were ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2094
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Unique serum anti-E1E2 antibodies were shown to be associated with spontaneous recovery or predictive of sustained virological response (SVR) in patients with chronic hepatitis C receiving pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. The objectives were to establish the relationship between pretreat...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2671
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Antibodies to liver-kidney microsome type 1 (anti-LKM-1), which are a marker of autoimmune hepatitis, are found in a minority of patients with chronic hepatitis C virus (HCV) infection. Whether interferon/ribavirin therapy is safe and effective in these patients is unclear. AIM:To describe the prevalence, c...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3-<36 months. METHODS:Children with stable HIV type-1 (HIV-1) RNA levels after 12 weeks...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3851/IMP1532
更新日期:2010-01-01 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
abstract::Combinations of two nucleoside analogue reverse transcriptase inhibitors plus a third agent represent the current standard for antiretroviral therapy. Stavudine is a nucleoside analogue that demonstrates in vitro activity against human immunodeficiency virus type 1 (HIV-1) and HIV-2 within an acceptable therapeutic in...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND:To investigate change in renal function in African patients initiating second-line antiretroviral therapy (ART) including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). METHODS:HIV-1-positive adults, failing standard first-line ART were randomized to either ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3097
更新日期:2017-01-01 00:00:00