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 understand the effect of N(t)RTIs on endogenous nucleotide pools. METHODS:The T-cell line CEM-CCRF was treated with control antimetabolites or the N(t)RTIs abacavir, didanosine, lamivudine, tenofovir (TFV) and zidovudine (AZT), either alone or in combination. The levels of natural 2'-deoxynucleoside triphosphates (dNTP) and ribonucleoside triphophosphates were determined by liquid chromatography coupled with triple quadrupole mass spectrometry. RESULTS:Antimetabolites altered nucleotide pools in a manner consistent with their known mechanisms of action. AZT was the only N(t)RTI that significantly altered dNTP pools. incubation of 10 microM AZT, either alone or in combination with other N(t)RTIs, increased 2'-deoxyadenosine triphosphate, 2'-deoxyguanosine triphosphate and thymidine triphosphate levels by up to 1.44-fold the concentrations observed in untreated cells. At higher than pharmacological concentrations of AZT, evidence for inhibition of 2'-deoxycytidylate deaminase and enzymes involved in the salvage of thymidine was also observed. Phosphorylated metabolites of TFV are known to inhibit purine nucleoside phosphorylase (PNP). However, in contrast to a potent PNP inhibitor, TFV was unable to alter intracellular dNTP pools upon addition of exogenous 2'-deoxyguanosine. CONCLUSIONS:N(t)RTIs have the potential to alter nucleotide pools; however, at the pharmacologically relevant concentrations, tested N(t)RTI or their combinations did not have an effect on nucleotide pools with the notable exception of AZT.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Vela JE,Miller MD,Rhodes GR,Ray ASsubject
Has Abstractpub_date
2008-01-01 00:00:00pages
789-97issue
6eissn
1359-6535issn
2040-2058journal_volume
13pub_type
杂志文章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::The current prevalence of cognitive impairment in HIV-infected individuals is surprisingly high, even in those with undetectable plasma HIV RNA. The aetiology is unknown but one possibility is inadequate control of persistent central nervous system (CNS) HIV infection. The CNS Penetration Effectiveness (CPE) rank has ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2951
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:The H275Y neuraminidase mutation conferring oseltamivir resistance has been reported in several pandemic A/H1N1 (pH1N1) isolates. We sought to evaluate transmission of this mutant virus through the direct contact and the airborne (aerosol and droplet) routes in the ferret model. METHODS:Groups of four ferre...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1794
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities. METHODS:We c...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2350
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Human cytomegalovirus (HCMV) infections remain a major problem in immunocompromised patients. Three antiviral agents, ganciclovir (GCV), foscarnet (FOS) and cidofovir (CDV), are currently approved for the treatment of HCMV infections. They all target the viral DNA polymerase and are associated with significa...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3028
更新日期:2016-01-01 00:00:00
abstract::Human papillomavirus (HPV) infections are a major human health problem; they are the cause of recurrent benign warts and of several cancers of the anogenital tract and head and neck region. Although there are two prophylactic HPV vaccines that could, if used universally, prevent as many as two-thirds of HPV-induced ca...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2612
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:To estimate the treatment and health care costs of HIV infection or AIDS in France during the era of highly active antiretroviral therapy (HAART). DESIGN:We used a clinical database of HIV-infected patients to calculate the resource use and cost of care for different stages of HIV infection. Costs were incor...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2002-12-01 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
abstract:BACKGROUND:Drug-resistant HBV mutants frequently arise during nucleoside/nucleotide analogue (NA) therapy, while the resistance mutations on polymerase also have consequent changes in the S protein. The enrichment of immune-escape mutations was negatively correlated with hepatitis B surface antigen (HBsAg) clearance un...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3156
更新日期:2017-01-01 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
doi:10.3851/IMP1931
更新日期:2011-01-01 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::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:HIV-1 shedding in genital secretions is associated with HIV transmission risk. Limited data exist on the effect of second-line lopinavir/ritonavir monotherapy (mLPV/r) on genital secretion of HIV RNA. METHODS:We measured HIV-1 in genital secretions of HIV-infected adults at time of failure from non-nucleosi...
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:OBJECTIVE:To evaluate, retrospectively, biochemical, serological and histological responses in chronic hepatitis B (CHB)-infected children who received combination therapy and continued with prolonged treatment with lamivudine (3TC). PATIENTS AND METHODS:CHB infection was defined as the presence of hepatitis B surface...
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
abstract:BACKGROUND:Increasing efavirenz (EFV) dose from 600 mg to 800 mg daily has been suggested with concomitant rifampicin (RFN), as induction of cytochrome P450 isoenzymes may reduce EFV plasma concentrations. METHODS:Individuals from the CIPRA-South Africa cohort taking EFV-based antiretroviral therapy with concomitant t...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:10.3851/IMP1780
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
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:Single-drug class regimens with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are generally not recommended as initial therapy because they are inferior compared with therapy with two NRTIs plus efavirenz. However, triple-NRTI combinations can be useful in specific circumstances such as in t...
journal_title:Antiviral therapy
pub_type: 杂志文章,meta分析,评审
doi:10.3851/IMP2726
更新日期:2014-01-01 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:Acute exacerbation (AE) in chronic hepatitis B (CHB) is usually followed by a spontaneous decline in HBV DNA levels. The subsequent treatment is controversial. In this study, we evaluated the efficacy and safety of pegylated interferon-α2a (PEG-IFN-α2a) for such CHB patients. METHODS:A total of 74 hepatitis...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2832
更新日期:2015-01-01 00:00:00
abstract::HIV-HBV-coinfected patients require optimal control of viral replication in order to prevent the development of severe comorbidities, such as liver cirrhosis and hepatocellular carcinoma. The genetic diversity of HBV is a poorly investigated factor of such viral replication in HIV-infected hosts. HBV genome diversity ...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1495
更新日期:2010-01-01 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 aim of this study was to assess the long-term efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS:A total of 272 antiretroviral-naive patients with a CD4+ T-cell count of 200-350 cells/mm3 were treated wit...
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: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:OBJECTIVES:Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We a...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:A high level of adherence to antiretroviral therapy is required for complete suppression of HIV replication, immunological and clinical effectiveness. We investigated whether cognitive behaviour therapy can improve medication adherence. DESIGN:Prospective randomized 1-year trial. SETTING:Collaboration of HI...
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:2004-02-01 00:00:00
abstract::Solid organ transplantation in HIV-infected individuals requires concomitant use of immunosuppressants and antiretrovirals that may cause significant drug interactions. Here we report on a peculiar pharmacokinetic interaction between tacrolimus and protease inhibitors (PIs) which occurred in four HIV-infected liver tr...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:To assess the baseline factors associated with haematological toxicity that lead to ribavirin or pegylated interferon (peginterferon) dosage reductions in hepatitis C and human immunodeficiency virus (HCV/HIV)-coinfected patients. DESIGN:Multicentre, prospective, observational study. SETTING:Eleven hospital...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2005-01-01 00:00:00
abstract::With the recent approval of several drugs for the management of chronic hepatitis B, the proper diagnosis and classification of this disease is necessary to determine if therapy is needed and what the best treatment options are. The diagnosis of chronic hepatitis B relies on serological testing, and disease stage is f...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Transmitted drug resistance (TDR) limits antiretroviral options and thus complicates the management of HIV-positive patients. HIV disproportionately affects the southern US, but available national estimates of TDR prevalence principally reflect large metropolitan centres outside this region. METHODS:The Duk...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00