Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as 'transcriptase inhibitors', 'protease inhibitors', 'integrase inhibitors' and the more recent 'fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C-C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed.
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PMID:The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies. 1925 Jan 35

The HIV replication cycle offers multiple targets for chemotherapeutic intervention, including the viral exterior envelope glycoprotein, gp120; viral co-receptors CXCR4 and CCR5; transmembrane glycoprotein, gp41; integrase; reverse transcriptase; protease and so on. Most currently used anti-HIV drugs are reverse transcriptase inhibitors or protease inhibitors. The expanding application of simulation to drug design combined with experimental techniques have developed a large amount of novel inhibitors that interact specifically with targets besides transcriptase and protease. This review presents details of the anti-HIV inhibitors discovered with computer-aided approaches and provides an overview of the recent five-year achievements in the treatment of HIV infection and the application of computational methods to current drug design.
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PMID:Therapeutic strategies underpinning the development of novel techniques for the treatment of HIV infection. 2009 4

Treatment of HIV infection currently presents a number of problems such as: a) Capacity choice of antiretrovirals used (classic and new), b) study of the emergence of resistance to them (molecular mechanisms of emergence of mutations agains treverse transcriptase, protease, integrase and CCR5 antagonists), c) high cost of drugs, as well as analytical testing or hospital incarnation, so palpable that expensive treatment; d) Information clinical application of tests of resistance, ie to whom and when tobe performed; e) Interpretation of genotype resistance, good clinical type (internal, external and cross), the fuzzy rules and fuzzy rules mathematics, neural networks (net neurat Works) or the different cohorts of resistance based on the development of databases.
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PMID:[Clinical indications for resistance testing HIV infection]. 2226 57

This study summarizes the adverse effects of antiretroviral therapy (ART) agents against HIV on orofacial health and health care. Current antiretroviral agents fall mainly into three major classes: nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) - now with the new classes of fusion inhibitors, entry inhibitors--CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. Many of the ART agents can have adverse orofacial effects, or can give rise to allergies or drug interactions--the optimum anti-HIV drug has yet to be found. There are few orofacial adverse effects that characterize a particular ART class, but erythema multiforme (EM), ulcers and xerostomia may be associated with reverse-transcriptase inhibitors (RTI); parotid lipomatosis, taste disturbance, xerostomia and perioral paraesthesia mainly related to PIs. Facial lipoatrophy is a common adverse effect of NRTIs; EM is more frequently associated with NNRTIs. Thus, although most of the more recent ART drugs and combinations of them show improved safety profiles, some may give rise to orofacial adverse effects, and may affect oral health care.
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PMID:Antiretroviral therapy: effects on orofacial health and health care. 2353 Aug 6

There are four classes of antiretroviral agents used in the treatment of HIV/AIDS. Adverse effects to Highly Active Antiretroviral Therapy (HAART) are common and often difficult to avoid. In many cases, research is not able to identify the exact cause of an adverse event. The severity of adverse reactions varies greatly and difficult to manage; typically prevention is more desirable than treatment. However, this is not always true. This paper will review safety aspect of class-wide Highly Active Antiretroviral Therapy, mechanism of action. A class-wide adverse effect for Reverse transcriptase inhibitors includes lactic acidosis, peripheral neuropathy and lipoatrophy. Class wide adverse effects to non-nucleoside reverse transcriptase inhibitors include rash and hepatotoxicity, while efavirenz has its own unique CNS reactions. Protease inhibitor side effects include hyperglycemia, lipoaccumulation, dyslipidemia, and gastrointestinal (GI) intolerance. Coreceptor CCR5 antagonists, which provide a novel mechanism of action, are a recent addition to the armamentarium of antiretroviral agents. Antiretroviral are an important break-through in the treatment of HIV/AIDS. However, adverse reactions from these drugs can range from mild to life-threatening, and determining which agent is the cause is frequently difficult to discern. Fortunately, side effects can be monitored, treated and in many cases, prevented.
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PMID:Safety Aspects of Antiretroviral Therapy for Management of HIV Infection. 2520 54

Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA <50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load <50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
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PMID:Efavirenz-Based Regimens in Antiretroviral-Naive HIV-Infected Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. 2593 4


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