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 analysed the cleavage sites p1/p7 and p1/p6-gag of 500 HIV-1 subtype B infected patients. The collective consists of 275 therapy-naive and 225 therapy-experienced patients with at least one primary PR mutation, from whom eight underwent therapy-interruption in different clinical settings. RESULTS:Multiple mutations within the CS p7/p1 and p1/p6-gag accumulated in therapy-experienced isolates (p7/p1: A431V-K436R-I437V and p1/p6-gag: L449F/V-P452S-P453L/A). Further rare CS mutations were totally absent in therapy-naive viruses. Sixty percent of all therapy-experienced viruses exhibited at least one therapy-associated CS mutation, but so did 10% of therapy-naive viruses. The analysis of CS and PR mutations in therapy-experienced viruses revealed several positive correlations--A431V with L24I-M46I/L-I54V-V82A; I437V with I54V-V82F/T/S; L449V with I54M/L/S/T/A; and L449F/R452S/P453L: with D30N-I84V--whereas P453L and V82A were negatively correlated. Mutagenetic trees constructed form this cross-sectional data showed an ordered accumulation of the most prominent CS mutations along two pathways L90M-I84V-P453L and I54-V82-A431V followed by either M46L or L24I. Furthermore, eight viruses with at least one therapy-associated mutation at each CS displayed an outstanding maintenance of major PR mutations during therapy interruption. CONCLUSIONS:These findings emphasize the relevance of CS mutations in the evolution of HIV resistance to PR inhibitors. Therefore, therapy-associated CS mutations should be considered in HIV resistance tests to estimate viral fitness in different clinical settings.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Verheyen J,Litau E,Sing T,Däumer M,Balduin M,Oette M,Fätkenheuer G,Rockstroh JK,Schuldenzucker U,Hoffmann D,Pfister H,Kaiser Rsubject
Has Abstractpub_date
2006-01-01 00:00:00pages
879-87issue
7eissn
1359-6535issn
2040-2058journal_volume
11pub_type
杂志文章abstract::In order to study the inhibitory effect of various reverse transcriptase inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro system, based on co-cultures of dendritic cells and resting CD4 T cells, modelling early target cells during sexual transmission. The compounds tested included the secon...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Little is known about non-adherence to HBV therapy. This study aimed to investigate the relationship between self-reported missed days of antiviral therapy and HBV virological breakthrough and factors associated with virological breakthrough. METHODS:A cross-sectional survey of 211 HBV patients receiving or...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP3087
更新日期:2017-01-01 00:00:00
abstract::P-glycoprotein (P-gp) limits bioavailability and accumulation of HIV protease inhibitors (PIs). PIs are ligands for the pregnane-X-receptor (PXR), which regulates P-gp expression. This occurs when ligands activate the receptor, initiating binding to response elements in the MDR1 promoter. PXR also activates cytochrome...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs) are the molecular entities that exert the therapeutic effects of medicines. This article provides an overview of the major APIs that are entered into antiretroviral therapy (ART), outlines how APIs are manufactured, and examines the regulatory and cost frameworks of manufacturi...
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:BACKGROUND:In vitro studies have reported controversial effects of protease inhibitors (PIs) on mitochondrially driven apoptosis. Additionally, since PIs in the clinical setting are almost always given in combination with nucleoside analogues, which may have negative effects on mitochondrial DNA (mtDNA), the impact of ...
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:Lamivudine (3TC) therapy can cause the emergence of M1841/V. Previous studies suggest a higher fidelity of the mutant reverse transcriptase and lower replication capacity of the mutant virus. No data exist from clinical comparative studies evaluating the benefit of M1841/V in patients receiving combination a...
journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2006-01-01 00:00:00
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 co...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Nucleoside transporter proteins (NTs) encoded by members of the SLC28 and SLC29 gene families contribute to nucleoside and nucleobase recycling but also modulate extracellular adenosine levels and thus adenosine-regulated metabolic targets. METHODS:We have examined the expression pattern of NT-encoding gene...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::There are many potential reasons for increased liver-related mortality in HIV-hepatitis B virus (HBV) coinfection compared with either infection alone. HIV infects multiple cells in the liver and might potentially alter the life cycle of HBV, although evidence to date is limited. Unique mutations in HBV have been defi...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2009-01-01 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:Alterations in endogenous nucleotide pools as a result of HIV therapy with nucleoside and nucleotide reverse transcriptase inhibitors (N[t]RTIs) is a proposed mechanism for therapy-related adverse events and drug interactions resulting in treatment failure. In vitro studies were performed in order to underst...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability. METH...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1540
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Cidofovir (CDV) is an acyclic nucleoside phosphonate that exhibits a potent antiviral activity against several DNA viruses. In previous studies, CDV has been shown to significantly reduce the clinical severity and the viral shedding in primary caprine herpesvirus type-1 (CpHV-1) infection in goats. CpHV-1 is...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1611
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:This study aimed to evaluate whether low darunavir (DRV) minimum plasma concentration (Cmin) values contribute to virological outcomes during DRV/ritonavir monotherapy (mtDRV/rtv). METHODS:This was a prospective observational single-arm 96-week efficacy study in virologically suppressed subjects on triple t...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2722
更新日期:2014-01-01 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
abstract:BACKGROUND:Scavenger receptor class B type-1 (SR-B1) is one of the many receptors used by HCV to infect hepatocytes. It is used by the virus not only to directly infect cells but also to facilitate cell-to-cell transmission of the virus. Agents such as anti-human SR-B1 (anti-hSR-B1) antibodies represent potential thera...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2570
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Lamivudine is widely used in patients with chronic hepatitis B virus (HBV) infection. In cirrhotic patients, long-term lamivudine therapy significantly reduced the risk of hepatocellular carcinoma (HCC). However, in a small but substantial portion of patients, HCC still developed despite lamivudine therapy. ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Few data are available about efficacy and durability of simplification from multi-tablet antiretroviral regimens to co-formulated efavirenz (EFV)/emtricitabine (FTC)/tenofovir (TDF) versus rilpivirine (RPV)/FTC/TDF in virologically suppressed HIV-1-infected patients. METHODS:We retrospectively analysed HIV-...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP3188
更新日期:2018-01-01 00:00:00
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 ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3344
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:The potential use of variola virus as a biological weapon has renewed efforts in the development of antiviral agents against orthopoxviruses. ST-246 [4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-di oxo-4,6-ethenocycloprop [f]isoindol-2(1 H)-yl)-benzamide] is an anti-orthopoxvirus compound active ag...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The nucleotide analogue, tenofovir, has been shown to lower plasma atazanavir levels in pharmacokinetic trials, an interaction that may be partly reversed by the addition of ritonavir, whereas plasma tenofovir levels are themselves raised when the drug is combined with lopinavir/ritonavir. OBJECTIVE:To inve...
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::Here, we describe a case of an HIV-infected patient with right lower limb oedema that appeared after initiation of tenofovir and emtricitabine treatment. The patient was fully investigated by serial heart and vessel echo-Doppler examination. Oedema of the lower limb was attributed to a transient drug-induced fivefold ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1302
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To assess the effect of interleukin (IL)-2 combined with highly active antiretroviral therapy (HAART) on HIV-1 pro-viral DNA quantification in HIV-1-infected patients with CD4<200/mm3. PATIENTS AND METHODS:Seventy patients with CD4<200 cells/mm3 and CV<1000 copies/ml were enrolled in a 6-month randomized con...
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:2003-06-01 00:00:00
abstract:BACKGROUND:The development of infections with ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) remains a serious problem in recipients of stem cell or organ transplants. Nearly all GCV-resistant clinical isolates have mutations in the viral UL97 gene. The rapid detection of GCV-resistant HCMV infections is nece...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Although antiretroviral therapy during pregnancy is associated with significant reductions in the risk of vertical transmission of HIV, attainment of this outcome in highly treatment-experienced pregnant women might be complicated by the lack of active drugs available to assemble a potent regimen. The recent...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1558
更新日期:2010-01-01 00:00:00
abstract::Treatment of primary human immunodeficiency virus (HIV) infection (PHI) may provide an opportunity to achieve a long lasting suppression of viral replication. Although there is growing evidence of the benefit of treating PHI, clinical data are still very limited. Special therapeutic considerations in this clinical set...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::HIV escape in the central nervous system (CNS) despite undetectable viral load in the plasma has been observed and may contribute to HIV-associated neurocognitive disorders. Favouring the use of HIV drugs with a good penetration into the CNS has been advocated, leading to the establishment of the CNS penetration-effec...
journal_title:Antiviral therapy
pub_type: 评论,杂志文章
doi:10.3851/IMP2561
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Two distinct inhibitors of the HCV protease have been approved for the treatment of patients infected with HCV genotype-1. These drugs are highly efficient in suppressing HCV replication; however, their use is limited by the emergence of viral mutants resistant to them after a very short time of treatment. B...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2326
更新日期:2013-01-01 00:00:00
abstract::Although zidovudine (ZDV) is effective in HIV-1-infected patients, the duration of its efficacy may be short when treatment is started in advanced HIV disease. This pilot prospective case-control study was designed to evaluate the combination of ZDV plus didanosine [ddI] compared with ZDV monotherapy as an initial the...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND:Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the ph...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP3198
更新日期:2018-01-01 00:00:00