Search results for "Nucleoside Reverse Transcriptase Inhibitor"
showing 10 items of 11 documents
Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort
2019
AbstractObjectivesTo evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017.Patients and methodsIn total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases…
Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease in…
2011
Abstract Background Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. Methods Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after…
Profile of leukocyte-endothelial cell interactions induced in venules and arterioles by nucleoside reverse-transcriptase inhibitors in vivo.
2013
Background There is controversy regarding cardiovascular (CV) toxicity of the nucleoside reverse-transcriptase inhibitors used to treat human immunodeficiency virus infection. Methods We evaluated the effects of nucleoside reverse-transcriptase inhibitors on leukocyte-endothelium interactions, a hallmark of CV diseases, in rat mesenteric vessels using intravital microscopy and in human arterial cells using a flow chamber system. Results Abacavir and didanosine increased rolling, adhesion and emigration in rat vessels. These effects were reversed with antibodies against Macrophage-1 antigen (Mac-1) or intercellular adhesion molecule 1 and were reproduced in human cells. Lamivudine, zidovudin…
Inhibition of Mitochondrial Function by Efavirenz Increases Lipid Content in Hepatic Cells
2010
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition. Given the importance of the liver in lipid regulation, we have evaluated the effects of clinically used concentrations of EFV on the mitochondria and lipid metabolism of human hepatic cells in vitro. Mitochondrial function was rapidly undermined by EFV to an extent that varied with the concentration employed; in particular, respiration and intracellular adenosine triphosphate (ATP) levels were reduced whereas reactive oxygen species (ROS) production i…
Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95
2013
The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease.Drugs were analysed in vitro in human cells (interactions of peripheral blood…
Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity
2011
Continuous administration of the drugs included under the term Highly Active Antiretroviral Therapy (HAART) has turned AIDS into a chronic disease, at least in developed countries (Panos et al., 2008). The initial development of these drugs was particularly rapid and focused on clinical efficacy before all other considerations. However, as the disease has come under control, there has been growing emphasis on the long-term adverse effects associated with this therapy. The first drug for the treatment of HIV infection, zidovudine (AZT), was approved in 1987. The number of other antiretroviral drugs already approved for use or under development continues to grow, and the primary aim of resear…
Adverse drug reactions to antiretroviral medication
2009
Antiretroviral therapy has greatly improved prognosis of HIV infection, with a dramatic reduction of morbidity and mortality worldwide. Nevertheless, the condition is still a common cause of death in many underdeveloped countries, where effective treatment is not always unavailable. More than 20 drugs active against HIV are commercially available, which belong to one of four groups: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion/entry inhibitors. In the near future new drugs are expected, including those of a novel group, the integrase inhibitors. To avoid viral resistance, combinations of the drugs must always b…
Patterns of transmitted HIV drug resistance in Europe vary by risk group
2014
BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM…
Transmission of drug-resistant HIV-1 in Europe remains limited to single classes
2008
BACKGROUND: The spread of drug-resistant HIV-1 might compromise the future success of current first-line regimens. OBJECTIVE: To analyse the extent and impact of transmission of drug-resistant HIV-1 variants in Europe. DESIGN AND METHODS: The European prospective programme (SPREAD) collected demographic, clinical and virological data from 1245 HIV-1-infected individuals in 17 countries diagnosed in 2002-2003. The potential impact of transmitted drug resistance mutations (TDRMs) on therapy response was determined by using genotypic interpretation algorithms. RESULTS: The overall prevalence of viruses with drug-resistance mutations was 9.1% [96/1050; 95% confidence interval: 7.5-11.1]. The ma…
No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy
2011
An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analy…