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 second-generation non-nucleoside RTI (NNRTI) TMC-120 (R147681, dapivirine) and TMC-125 (R165335, travertine), as well as the reference nucleoside RTI AZT (zidovudine), the nucleotide RTI PMPA (tenofovir) and the NNRTI UC-781. The virus strains included the reference strain HIV-1Ba-L and six primary isolates, representative of the HIV-1 group M pandemic. They all display the non-syncytium-inducing and CCR5 receptor-using (NSI/R5) phenotype, important in transmission. Cell-free virus was immobilized on a poly-L-lysine (PLL)-treated microwell plate and incubated with compound for 1 h. Afterwards, the compound was thoroughly washed away; target cells were added and cultured for 2 weeks, followed by an extended culture with highly susceptible mitogen-activated T cells. Viral production in the cultures was measured on supernatant with HIV antigen ELISA. Negative results were confirmed by showing absence of proviral DNA in the cells. TMC-120 and TMC-125 inhibited replication of HIV-1Ba-L with average EC50 values of 38 nM and 117 nM, respectively, whereas the EC50 of UC-781 was 517 nM. Complete suppression of virus and provirus was observed at compound concentrations of 100, 300 and 1000 nM, respectively. Inhibition of all primary isolates followed the same pattern as HIV-1Ba-L. In contrast, pre-treating the virus with the nucleotide RTI PMPA and AZT failed to inhibit infection even at a concentration of 100000 nM. These data clearly suggest that NNRTIs inactivate RT enzymatic activity of different viral clades (predominant in the epidemic) and might be proposed for further testing as a sterilizing microbicide worldwide.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Njai HF,Lewi PJ,Janssen CG,Garcia S,Fransen K,Kestens L,Vanham G,Janssen PAsubject
Has Abstractpub_date
2005-01-01 00:00:00pages
255-62issue
2eissn
1359-6535issn
2040-2058journal_volume
10pub_type
杂志文章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:There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B. METHODS:We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on la...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2335
更新日期:2012-01-01 00:00:00
abstract::A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 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:We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS:The prevalence of DRV RAMs, identified from IAS 2010 an...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2015
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. The aim of this study was to analyse the prevalence and predi...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3140
更新日期:2017-01-01 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::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: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:Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characte...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2749
更新日期:2014-01-01 00:00:00
abstract::HIV drug resistance testing is becoming an integral part of antiretroviral drug development and of patient management. The parameters that characterize the performance of both phenotypic and genotypic assays and the validation of this performance are essential to their proper use for these applications. Several princi...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVES:To characterize 1-year virological response to antiretroviral therapy and its determinants by sex. METHODS:This is a population-based analysis of antiretroviral therapy naive HIV-positive adult men and women. Factors associated with sex and with plasma HIV RNA viral load suppression to below 500 copies/ml w...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens. METHODS:We used data from the Swiss HIV Cohort Study to estimate the effectiveness of two new dolutegravir dual regimens relative to the...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3310
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:We sought to determine whether markers of systemic inflammation are associated with the presence of moderate/severe obstructive sleep apnea (OSA) and whether this association differs based on HIV and HIV treatment status. METHODS:HIV-uninfected men (HIV-; n=60), HIV-infected men receiving HAART (HIV+/HAART;...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP2745
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Ageing HIV-infected patients present an increased incidence of cardiovascular diseases, endothelial dysfunction being an early alteration. Some protease inhibitors (PIs) have been shown to increase the risk of cardiovascular disease. We evaluated here the effects of CCR5 or integrase inhibitors as compared t...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3160
更新日期:2017-01-01 00:00:00
abstract::Antiretroviral treatment with three nucleoside reverse transcriptase inhibitors (NRTIs) is widely used, but the combination of abacavir, didanosine and stavudine has never been investigated. We describe the surprising and consistent genotypic and phenotypic outcome in patients failing this combination. As part of a Da...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:Hepatitis C virus genotype 1B responds poorly to treatment with interferon, in contrast to the more interferon-sensitive genotypes 2 and 3. Studies on combination therapy regimens with PEG-interferon and ribavirin report sustained response rates that generally do not exceed 50%, in contrast to sustained resp...
journal_title:Antiviral therapy
pub_type: 杂志文章,meta分析
doi:
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:The objective of this study was to compare indinavir peak plasma (Cmax) values after administration of indinavir/ritonavir 800/100 mg on an empty stomach or with food. High indinavir Cmax values have been associated with indinavir-related nephrotoxicity. METHODS:This was an open-label, randomized, two-treat...
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:2003-08-01 00:00:00
abstract:BACKGROUND:Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1509
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine th...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1630
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Zika virus, a previously neglected mosquito-borne virus, is prompting worldwide concern because of its connection with congenital defects, Guillain-Barré syndrome, meningoencephalitis and myelitis in infected individuals. However, no specific antiviral therapy is available at present. In this study, we inves...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3180
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:In patients with chronic HCV infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, has been reported. The aim of this study was to investigate the association of IR ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2743
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND/AIMS:The role of antibody in hepatitis C virus (HCV) infection remains unclear although many reports attest to its role in viral clearance. Here we describe epitopes that are recognized by antibody present in the serum of infected patients and show that such epitopes can induce neutralizing antibodies. METH...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract::We assessed the prevalence and clinical impact of insertions within the HIV-1 p6Gag proline-rich (PTAP) region on initial antiretroviral therapy response in 461 HIV-infected, drug-naive individuals initiating therapy in British Columbia, Canada between June 1996 and August 1998. HIV p6Gag insertions were detected by n...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS:A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 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: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
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