Search results for "Reverse Transcriptase Inhibitor"

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…

Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.

2015

ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…

Twenty Years of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Time to Reevaluate their Toxicity

2011

Twenty years of effective clinical application have consolidated non-nucleoside reverse transcriptase inhibitors (NNRTI) as essential components of the Highly Active Antiretroviral Therapy (HAART) employed in the treatment of Human Immunodeficiency Virus (HIV). However, as the disease has come under control, there has been growing emphasis on the long-term adverse effects induced by this chronic pharmacological therapy. Although traditionally considered to be safe and well-tolerated drugs, there is mounting evidence that associates NNRTI with the onset of cutaneous reactions, neuropsychiatric symptoms, hepatotoxicity, metabolic disturbances and gastrointestinal toxicity. Though the clinical…

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…

Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation

2010

Objective: Abacavir and didanosine are nucleoside reverse transcriptase inhibitors (NRTI) widely used in therapy for HIV-infection but which have been linked to cardiovascular complications. The objective of this study was to analyze the effects of clinically relevant doses of abacavir and didanosine on human leukocyte―endothelium interactions and to compare them with those of other NRTIs. Design and methods: The interactions between human leukocytes ― specifically peripheral blood polymorphonuclear (PMN) or mononuclear (PBMC) cells ― and human umbilical vein endothelial cells were evaluated in a flow chamber system that reproduces conditions in vivo. The expression of adhesion molecules wa…

How long to treat chronic hepatitis B virus infection with lamivudine?

2000

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…

Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop

2011

Abstract The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as “possible”, “optional” or “mandatory” according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the…

Fibrosis in chronic viral hepatitis

2011

In the last years, several studies have been performed with the aim to evaluate the real impact of antiviral treatments on fibrosis progression in patients with chronic viral hepatitis. The main goal of therapy in patients with chronic hepatitis B is viral suppression. This outcome leads to an important improvement in both hepatic inflammation and fibrosis and reduces the HCC occurrence. An histological improvement has been largely demonstrated in patient treated with oral nucleoside and nucleotide analogs achieving the rate of 72% with entecavir and tenofovir. Similarly, in patients with chronic hepatitis C, sustained virologic response to interferon therapy is associated with regression o…

In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats

2018

Abstract Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (Ki …