Search results for "Reverse Transcriptase Inhibitor"
showing 10 items of 50 documents
Transmission of Drug-Resistant HIV Type 1 Strains in HAART-Naive Patients: A 5-Year Retrospective Study in Sicily, Italy
2010
The transmission of drug-resistant HIV-1 strains might compromise the efficacy of current first-line antiretroviral (ARV) regimens. Between 2004 and 2008, HIV-1 reverse transcriptase (RT) and protease (PR) genes of 108 ARVnaive Sicilian patients were amplified and sequenced to describe the prevalence of ARV resistance mutations among HAART-naive HIV-1-infected individuals. The frequency of transmitted drug resistance mutations (DRAMs) was determined by using genotypic interpretation algorithms. The proportion of HAART-naive HIV- 1-infected patients in Sicily increased from 18.4% to 23.5% during 2004–2008. Among naive patients, the overall prevalence of DRAMs was 15.7% [17/108; 95% CI: 9.4–2…
[Correlation, in previously treated HIV-1 positive patients, between hypersensitivity reaction to abacavir and the presence of the HLA-B*5701 allele].
2009
Abstract Introduction Hypersensitivity reaction to abacavir (a powerful inverse transcriptase inhibitor) is a serious adverse effect that limits its use in antiretroviral treatment and requires a high level of clinical surveillance. Certain haplotypes of the primary histocompatibility complex proteins (HLA-B*5701) are very significant predictors of the risk of hypersensitivity to this drug. The purpose of this study is to identify the cases where a probable hypersensitivity reaction to abacavir presented the HLA-B*5701 allele. Method A retrospective study was conducted in all HIV-1 positive adult patients infected treated with abacavir between January 2000 and December 2007, in Department 6…
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-co…
2008
Background: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. Methods: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely…
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…
Synthesis of new 2,3-diaryl-1,3-thiazolidin-4-ones as anti-HIV agents
2004
Several 2,3-diaryl-1,3-thiazolidin-4-ones were synthesized and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of HIV-1 replication at 30-50 nM concentrations with minimal cytotoxicity, thereby acting as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).
Neuronal Bioenergetics and Acute Mitochondrial Dysfunction: A Clue to Understanding the Central Nervous System Side Effects of Efavirenz
2014
Background. Neurological pathogenesis is associated with mitochondrial dysfunction and differences in neuronal/glial handling of oxygen and glucose. The main side effects attributed to efavirenz involve the CNS, but the underlying mechanisms are unclear. Methods. Human cell lines and rat primary cultures of neurons and astrocytes were treated with clinically relevant efavirenz concentration. Results. Efavirenz alters mitochondrial respiration, enhances reactive oxygen species generation, undermines mitochondrial membrane potential, and reduces adenosine triphosphate (ATP) levels in a concentration-dependent fashion in both neurons and glial cells. However, it activates adenosine monophospha…
Autophagy as a rescue mechanism in efavirenz-induced mitochondrial dysfunction: a lesson from hepatic cells.
2011
Efavirenz (EFV) is the most widely used non-nucleoside reverse transcriptase inhibitor applied in highly active antiretroviral therapy (HAART), the combined pharmacological treatment of the human immunodeficiency virus infection. Its use has been associated with the development of several adverse events including hepatotoxicity. The molecular pathogenesis of this effect is poorly understood but recent reports have highlighted features of mitochondrial dysfunction in hepatic cells exposed to clinically relevant concentrations of EFV. In this study, we investigated the activation of autophagy and, in particular, mitophagy, in human hepatic cells exposed to EFV. We detected the presence of alt…
ER stress in human hepatic cells treated with Efavirenz: Mitochondria again
2013
Background & Aims ER stress is associated with a growing number of liver diseases, including drug-induced hepatotoxicity. The non-nucleoside analogue reverse transcriptase inhibitor Efavirenz, a cornerstone of the multidrug strategy employed to treat HIV1 infection, has been related to the development of various adverse events, including metabolic disturbances and hepatic toxicity, the mechanisms of which remain elusive. Recent evidence has pinpointed a specific mitochondrial effect of Efavirenz in human hepatic cells. This study assesses the induction of ER stress by Efavirenz in the same model and the implication of mitochondria in this process. Methods Primary human hepatocytes and Hep3B…
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…
Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults
2015
Objective: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. Design: Observational European cohort collaboration study. Methods: Eligible patients were antiretroviral-naive with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load ( 50 copies/ml) after initial s…