Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz (Sustiva), was added to the Department of Health and Human Services' (DHHS) "Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents" as a preferred component of combination anti-HIV therapy, in 1998. Efavirenz is the first non-protease inhibitor drug to be included as a preferred agent. The other NNRTIs, nevirapine and delavirdine, are included as "alternative" recommendations. More information was added to the guidelines, including adverse effects of anti-HIV drugs and drug resistance testing. A web address for the full guidelines is provided.
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PMID:Government updates HIV treatment guidelines. 1136 34

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of patients with HIV infection. Both US and British treatment guidelines for HIV infection recommend NNRTI- or protease inhibitor-based combinations [i.e. with nucleoside reverse transcriptase inhibitors (NRTIs)] as first-line treatmentoptions in the management of HIV disease. Results of a pivotal randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection (the majority of whom were antiretroviral therapy-naive) showed the efavirenz-based regimen was better tolerated and had greater success in achieving reductions in viral load below the limit of detection. These and other clinical data were incorporated into economic models in 2 analyses, one conducted in the US and the other in Canada. The US analysis examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy. The efavirenz-based regimen was the dominant treatment strategy as it was predicted to improve survival and reduce direct medical costs in the US healthcare system. Compared with the indinavir-containing regimen, survival was increased by 11% (absolute difference) and cumulative costs were reduced by $US10,326 per patient (1998 discounted costs) at 5 years after starting treatment with efavirenz-based therapy. The Canadian analysis was conducted from the perspective of the Ontario healthcare system. This study did not consider differences in clinical efficacy between treatment groups, costs of study medication or outcomes beyond 1 year--all factors that would have favoured the efavirenz-based regimen. Of the 2 treatment options, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs, primarily because of greater costs associated with adverse clinical events with the indinavir-based regimen. In conclusion, current treatment guidelines for HIV infection recognise efavirenz-based combination regimens as a first-line treatment option. A pivotal comparative clinical trial (DMP 266-006) showed a significantly greater virological response to efavirenz- than indinavir-based triple combination therapy, and the efavirenz-based regimen was better tolerated. These clinical data are supported by pharmacoeconomic analyses conducted in the US and Canada, both of which showed lower medical care costs with the efavirenz-based regimen. The US analysis also predicted long term health benefits, such as improved survival, with efavirenz- versus indinavir-based triple combination therapy. These results must be weighed against the inherent difficulties of predicting long term treatment failure rates from short term data, and the limited number of pharmacoeconomic analyses conducted with efavirenz to date.
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PMID:Efavirenz: a pharmacoeconomic review of its use in HIV infection. 1138 58

The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV-infected person presented with two severe melancholic episodes associated with marked cognitive disorders which resisted two successive antidepressant treatments (viloxazine and citalopram, respectively) prescribed at effective doses and for sufficient time duration. Mister H. had no personal or family psychiatric antecedent. His psychic condition improved only when efavirenz was discontinued. However, drug discontinuation may not be an obligatory step to improve the patient's condition since antidepressant treatment has been found effective in some similar situations. Actually, each case should be discussed with the clinicians taking care of the patient.
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PMID:[Apropos of atypical melancholia with Sustiva (efavirenz)]. 1148 60

(1) Efavirenz, a non nucleoside HIV reverse transcriptase inhibitor, is indicated, in combination with other antiretroviral drugs, for the treatment of HIV infection. (2) The methodologically sound clinical file is limited to trials based on validated surrogate end points (viral load) and involving patients in the early stages of HIV infection. (3) Two dose-finding studies favour a dose regimen of 600 mg in a single daily intake for adults. (4) Interim results of three ongoing trials are also available. After 48 weeks of treatment, three-drug regimens comprising efavirenz plus two nucleoside inhibitors were more effective on viral load than three-drug regimens comprising indinavir plus two nucleoside inhibitors. In another trial, after 24 weeks of treatment, a three-drug regimen combining efavirenz and two nucleoside inhibitors was no more effective on viral load than a three-drug regimen comprising nelfinavir and two nucleoside inhibitors. (5) It remains to be determined if four-drug regimens comprising efavirenz, a protease inhibitor and two nucleoside inhibitors are superior to three-drug regimens. (6) Data on the safety profile of efavirenz show mainly neuropsychological and cutaneous disorders. The severity of cutaneous effects in children needs further assessment.
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PMID:Efavirenz: new preparation. An alternative to HIV protease inhibitors. 1150 86

Efavirenz is a potent non-nucleoside reverse transcriptase inhibitor, licensed for the treatment of HIV-1. Data on sanctuary site penetration are limited. Therefore, we measured efavirenz concentrations in the blood and semen of 19 HIV-1-positive men and found concentrations in seminal plasma averaged 10% of those in blood plasma. Furthermore, seminal plasma viral loads were suppressed by 24 weeks of therapy in all patients. These data suggest that efavirenz-containing regimens have antiviral activity within the male genital tract.
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PMID:Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men. 1160 Aug 38

Efavirenz is a non-nucleoside reverse transcriptase inhibitor for the treatment of the HIV infection. A simple, high-performance liquid chromatographic method has been developed and validated for the quantitative determination of efavirenz in human plasma. The method involved solid-phase extraction of the drug and the internal standard (L-737,354) from 300 microl of human plasma. The analysis was via UV detection at 250 nm using a reversed-phase C8 analytical column and a isocratic mobile phase consisting of phosphate buffer (pH 5.75)-acetonitrile that resolved the drug and internal standard from endogenous matrix components and potential coadministered drugs. Within- and between-day precisions were less than 8.6% for all quality control samples. The lower limit of quantification was 0.1 microg/ml. Recovery of efavirenz from human plasma was greater than 83%. This validated assay is being used in pharmacokinetic studies with efavirenz.
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PMID:Determination of efavirenz in human plasma by high-performance liquid chromatography with ultraviolet detection. 1171 May 83

Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) develops quickly and independently if they are used in combination with NRTIs or protease inhibitors (PIs) as rescue therapy, mainly due to the low genetic barrier of this class of drugs. In this study we examined clinical, therapeutic, and virologic characteristics in 88 patients with mutations conferring resistance to NNRTIs, and in 11 patients 1 year after stopping NNRTI therapy. Between patients administered Nevirapine (NVP) and those taking Efavirenz (EFV), no statistical differences were found in CD4 cell count, HIV viral load, time on NNRTI therapy, or number of PIs administered previously. A slow decline in the detectability of mutations encoding NNRTI resistance was found.
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PMID:Genotype resistance profiles in patients failing an NNRTI-containing regimen, and modifications after stopping NNRTI therapy. 1194 95

Efavirenz and a series of related quinazolinone nonnucleoside inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) were evaluated in a series of two-drug combinations with several nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), and protease inhibitors (PIs). These combinations were tested in an established HIV-1 RT enzyme assay and a cell-based yield reduction assay with HIV-1 (replicative form [RF])-infected MT-2 cells. Synergy, additivity, and antagonism were determined in the two different assay systems by the method of Chou and Talalay (T.-C. Chou and P. Talalay, Adv. Enzyme Reg. 22:27-55, 1984). Efavirenz, DPC082, DPC083, DPC961, and DPC963 used in combination with the NRTIs zidovudine and lamivudine acted synergistically to inhibit RT activity in the HIV-1 RT enzyme assay and additively to slightly synergistically to inhibit HIV-1 (RF) replication in the yield reduction assay. The five NNRTIs in combination with the PI nelfinavir acted additively in the yield reduction assay to inhibit HIV-1 replication. Interestingly, efavirenz in combination with a second NNRTI acted additively to inhibit HIV-1 RT function in the enzyme assay, while it acted antagonistically to inhibit HIV-1 (RF) replication in the yield reduction assay. These data suggest that antiretroviral combination regimens containing multiple NNTRIs should be given thorough consideration before being used.
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PMID:Potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other human immunodeficiency virus NNRTIs, NRTIs, or protease inhibitors. 1201 69

Efavirenz is a nonnucleoside reverse transcriptase inhibitor that can be given with other antiretroviral agents for the treatment of human immunodeficiency virus infection. A 47-year-old man with acquired immunodeficiency syndrome developed severe depression and suicidal ideation necessitating psychiatric hospitalization and antidepressant therapy. The symptoms occurred in temporal relation to the introduction of efavirenz into his highly active antiretroviral therapy regimen. Similar serious psychiatric adverse effects have been associated with this agent. Clinicians should monitor for central nervous system adverse effects in all patients taking efavirenz.
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PMID:Central nervous system adverse effects with efavirenz: case report and review. 1212 26

Efavirenz and nevirapine are non-nucleoside reverse transcriptase inhibitors for the treatment of HIV-1-infected individuals. A simple and rapid high-performance liquid chromatographic method for the simultaneous quantification of efavirenz and nevirapine in human plasma suitable for therapeutic drug monitoring is described. Sample pre-treatment consisted of protein precipitation with acetonitrile and subsequently dilution with distilled water. The drugs were separated from endogenous compounds by isocratic reversed-phase high-performance liquid chromatography with ultraviolet detection at 275 nm. The method was validated over the therapeutically relevant concentration range of 0.05-15.0 mg l(-1) and 0.25-15.0 mg l(-1) for efavirenz and nevirapine, respectively, using a volume of 100 microl of plasma. The calibration curves were linear over this concentration range. Carbamazepine was used as internal standard. The assay proved to be accurate (accuracies varied between -12.7 and 8.5%) and precise (intra- and inter-assay precisions were less then 5.9%). The tested batches of control human plasma and frequently co-administered drugs did not interfere with the described methodology. Efavirenz and nevirapine were stable under various relevant storage conditions. This validated assay is suited for use in pharmacokinetic studies with efavirenz and nevirapine and can readily be implemented in the setting of a hospital laboratory for the monitoring of efavirenz and nevirapine concentrations.
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PMID:Simple and rapid method for the simultaneous determination of the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine in human plasma using liquid chromatography. 1286 43


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