Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active antiretroviral therapy has significantly reduced HIV-related morbidity and mortality. Increasingly, fixed-dose antiretroviral combinations with equal or greater potency than traditional antiretrovirals, along with fewer side effects, reduced toxicity, and simplified dosing convenience are being utilized. Tenofovir-emtricitabine (TDF-FTC) represents one of the more recent fixed-dose combinations. In combination with either a ritonavir-boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, TDF-FTC is a preferred choice in recent treatment guidelines on the basis of demonstrated potency in randomized clinical trials, one-pill-a-day dosing convenience, and relatively low toxicity. In addition, the drug is active against hepatitis B virus. Caution must be exercised in patients with renal insufficiency, or when the drug is used with certain other drugs. This manuscript reviews the use of TDF-FTC in the treatment of HIV.
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PMID:Review of tenofovir-emtricitabine. 1851 68

Tenofovir is a nucleotide analogue and consequently its mechanism of action differs from that of nucleoside analogues. This drug is administered orally in the form of disoproxil ester, which is deesterified to achieve a bioavailability of more than 20%. This bioavailability slightly increases if tenofovir is taken with a fat-rich meal. This drug has broad tissue distribution, aided by its small molecular size and very low protein binding, and is eliminated as unchanged drug in the urine through glomerular filtration and active tubular secretion. Because of this latter characteristic, dosage adjustments are required in patients with renal insufficiency. The intracellular half-life of tenofovir is more than 10 times greater than the plasma half-life. Because of the pharmacokinetic profile of tenofovir, interactions with other drugs are scarce. Within the class of antiretroviral agents, an increase in the bioavailability of didanosine has been described, leading to the recommendation that the dose of didanosine be reduced when used in combination with tenofovir. Tenofovir can be used without adjustments with other nucleoside and nonnucleoside reverse transcriptase inhibitors. Equally, tenofovir seems to have no effect on the pharmacokinetics of protease inhibitors although these latter agents may produce a slight increase in the bioavailability of tenofovir, which seems to be of little clinical relevance. The absence of interactions with other non-antiretroviral agents has been reported.
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PMID:[Tenofovir: pharmacology and interactions]. 1919 31

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding these findings suggest that the augmented stimulation of the host response to unabated viral replication may contribute to these comorbidities. Increased expression of chemokine receptor 5 and proinflammatory cytokines, disruption of immune cell function, and reduction in key inflammatory cells have been studied as potential mechanisms. Additionally, the increased inflammatory response has been shown to increase intracellular levels of nucleoside and nucleotide reverse transcriptase inhibitors, resulting in increased toxic manifestations. Structured treatment interruptions should be avoided in the management of HIV-infected individuals.
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PMID:Antiretroviral treatment interruptions and risk of non-opportunistic diseases. 1935 78

The choice of antiretroviral treatment in comorbidities requires thorough knowledge of the interactions, pharmacokinetics and adverse effects of the drug to be used. Most drugs carry some risk in certain processes associated or not with HIV infection and drugs that can be used in these situations are of great interest. The development of etravirine, a new non-nucleoside reverse transcriptase inhibitor, will allow its use in these processes, with a lower risk of secondary effects and therefore of worsening the course of the disease and of treatment withdrawal. This is the case of patients coinfected with active hepatitis B and/or C virus and patients with a history of psychiatric disorders or receiving psychotropic drugs. The possible use of etravirine in women of fertile age is also of interest, due to the lower risk of teratogenicity if pregnancy occurs during treatment. Other collectives, such as patients with renal insufficiency or children and adolescents should not be forgotten; although these populations are less well studied, data are beginning to become available.
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PMID:[Etravirine in special populations]. 2011 27

The remarkable advances in interferon-sparing, all-oral hepatitis C virus (HCV) treatment were a highlight of the 2014 Conference on Retroviruses and Opportunistic Infections (CROI). The backbone of the nucleotide inhibitor sofosbuvir and the nonstructural protein 5A (NS5A) inhibitor ledipasvir with an additional third agent (HCV protease inhibitor or HCV nonnucleoside reverse transcriptase inhibitor) led to a sustained virologic response (SVR) rate 12 weeks after cessation of treatment of 95% to 100% after only 6 weeks of treatment. These results demonstrate the potential of combination directacting antiviral (DAA) therapy for abbreviated, well-tolerated, and highly effective HCV treatment. Two triple-drug regimens that comprised 12 weeks of an NS5A inhibitor, an HCV protease inhibitor, and a nonnucleoside inhibitor also resulted in SVRs of more than 90% in patients with HCV genotype 1. HIV coinfection does not appear to negatively impact response to DAA-based HCV therapy, as evidenced by similar response rates in HIV/HCV-coinfected patients compared with HCV-monoinfected patients receiving interferonsparing or -containing regimens. There was continued emphasis at CROI 2014 on non-AIDS complications of HIV infection, specifically cardiovascular disease, renal insufficiency, and bone and endocrine disorders that persist among patients with treated HIV disease and contribute to morbidity and mortality. Finally, new data on novel drugs and combinations for treatment of tuberculosis (TB), patient outcomes using new rapid TB diagnostics, and a short-course TB prevention strategy were presented.
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PMID:CROI 2014: Viral hepatitis and complications of HIV disease and antiretroviral therapy. 2490 86

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor discovered in the USA in 2001. It is currently the treatment of choice for patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus. Its antiretroviral efficacy and good tolerance are responsible for the higher frequency of prescriptions compared with other nucleoside analogs. However, it can induce acute renal toxicity causing impairment of the proximal tubular function of the kidney. This is highly dependent on factors such as associated co-prescription didanosine or a protease inhibitor "boosted" with ritonavir, preexisting renal insufficiency, low body weight, or presence of associated diabetes. In contrast, long-term renal toxicity remains highly debated. Some studies describe a decrease in estimated glomerular filtration rate during prolonged treatment with TDF. Others reported renal safety even during prolonged use. The differences between patients enrolled in the different studies, the measured parameters and their interpretation could explain these discrepancies. We describe a case of a patient infected with HIV, who presented with Fanconi syndrome with acute renal failure six months after starting antiretroviral treatment including tenofovir.
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PMID:Fanconi syndrome induced by tenofovir: A case report. 2742 4


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