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

DuPont Pharmaceuticals and Glaxo Wellcome began marketing two new drugs, and the pricing of the drugs started a controversy. DuPont's efavirenz (Sustiva) was priced 60 percent higher than any other nonnucleoside reverse transcriptase inhibitor (NNRTI), with an annual retail price close to $5,000. In response, an ad hoc coalition called the Fair Price Working Group circulated a consensus statement demanding that the drug be priced like other drugs in that category. DuPont refused to reconsider, citing potency, once-daily dosing, and development costs. Several of the largest AIDS Drug Assistance Programs (ADAPs) also refused to add efavirenz to their formularies even though Dupont offered ADAPs a 5 percent rebate on the drug. Glaxo Wellcome learned from this dispute and priced its nucleoside analog abacavir at a level that ADAPs could afford, even though it is at the high end for its class of drugs. The coalition commended Glaxo for fairness in its pricing decision. Agouron and Bristol-Myers Squibb have also been criticized for repeatedly raising prices on their drugs. A continuing dialog, prior to price setting, will lead to greater understanding of a company's costs and may improve a company's reputation.
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PMID:Soaring prices, soaring sales. 1136 20

More than 100 HIV-related groups, including ACT UP, have endorsed the Fair Pricing Consensus Statement, which requires DuPont to reduce the price of its non-nucleoside reverse transcriptase inhibitor (NNRTI) Sustiva. Sustiva costs nearly twice as much as other NNRTIs. This high cost makes it difficult for programs to support the drug and for individuals to afford it.
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PMID:The high cost of fighting HIV. 1136 35

DuPont Pharmaceuticals' Sustiva (efavirenz) was approved by the FDA as the first once-daily- dosing anti-HIV drug. Sustiva is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and should always be used in conjunction with other antiretrovirals. Contact information is provided.
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PMID:Now approved: Sustiva in combination offers patients a new first-line therapy. 1136 40

Research presented at the 6th Conference on Retroviruses and Opportunistic Infections suggests that highly active antiretroviral therapy (HAART) does not have to include protease inhibitors to be effective. Other drug combinations should achieve positive results; the potency of the drug combination is the most important. Two 48-week trials, one including the non-nucleoside reverse transcriptase inhibitor Sustiva (efavirenz) and the other consisting of all nucleoside reverse transcriptase inhibitors, have shown that a protease-sparing regimen can be just as potent and durable. These regimens are even more attractive because of lower prices and the lack of side effects associated with protease inhibitors. The results of these two studies will give clinicians more HAART options.
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PMID:A new HAART on the horizon says the proof is in the potency. 1136 18

A non-nucleoside reverse transcriptase inhibitor, Sustiva (efavirenz, formerly DMP 266), received FDA approval for use by children and adults. Dosing is recommended at bedtime to avert side effects, which are described. People who receive the drug should avoid driving. Women should not become pregnant while taking this medication. Triple combination therapy with Sustiva and AZT/ Epivir (3TC) may be as effective as the combination of Crixivan with AZT/Epivir (3TC), preliminary trials showed. The drug costs about $4,000 a year. Contact information for obtaining financial assistance in the purchasing the drug is provided.
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PMID:Sustiva (efavirenz) is approved. 1136 71

The Food and Drug Administration recently approved efavirenz (Sustiva), a non-nucleoside reverse transcriptase inhibitor (NNRTI), for use in treatment of adults and children. When used in combination therapy, efavirenz has shown to be very effective in suppressing viral loads for a minimum of 24 weeks. People taking efavirenz should be aware of potential cross-resistance with the other two approved NNRTIs, Nevirapine and Delavirdine, as well as possible drug interactions. Common side effects and dosing information are described. Because of the high cost, efavirenz may not be covered under some States' AIDS Drug Assistance Programs (ADAPs). The Access Project can provide the numbers of State ADAP coordinators for further information, or individuals may contact Dupont Pharma's Patient Assistance Program at the number provided.
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PMID:Efavirenz (Sustiva) receives FDA approval. Food and Drug Administration. 1136 87

Protease-sparing regimens are sometimes considered the best initial therapy because they can effectively reduce viral load, while allowing the individual to reserve potent protease inhibitor therapy for later treatment. Others contend that the more potent therapy should be used first, to give a patient the best shot at long-term viral suppression. The debate continues with the promotion of efavirenz (Sustiva), a non-nucleoside reverse transcriptase inhibitor (NNRTI), sometimes prescribed as the initial course of therapy. Several reasons are explored for re-evaluating this decision, which is largely based on limited information from one trial with significant results. A table compares efavirenz with Nevirapine and Delavirdine, two other NNRTIs. There are still not enough data to support a recommendation about the use of protease-sparing treatment or the comparative value of the three NNRTIs listed.
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PMID:Strategy update: protease-sparing regimens. 1136 90

None of the studies conducted on people who have reduced the number of antivirals taken in their regimen have shown good results. Research has consistently shown that these people have an increased viral load count when one or more drugs are discontinued. Results from a French study show some promise in switching from a protease inhibitor to a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) such as Viramune (Nevirapine) or Sustiva (efavirenz). Fifteen out of sixteen participants maintained viral load levels below 200 copies when they changed to an NNRTI regimen. The one person whose viral load increased had taken an NNRTI drug before, although its use was prohibited in eligibility requirements. The strategy may work for people at varying stages of the disease, but larger studies are needed to confirm the results. Also, a fifth protease inhibitor, Amprenavir (Agenerase) has received FDA approval. Trial results are summarized, and side effects and drug interactions with Amprenavir are described.
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PMID:New treatment options. 1136 13

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

It was previously found that certain nonnucleoside reverse transcriptase inhibitors (NNRTI) possess virucidal activity against human immunodeficiency virus type 1 (HIV-1), and it was suggested that the tight-binding mode of inhibition of reverse transcriptase might be important for this virucidal activity (Borkow et al., J. Virol. 71:3023-3030, 1997). To test this, we compared six different NNRTI, including three tight-binding NNRTI, namely UC781, efavirenz (EFV) (Sustiva), and 5-chloro-3-phenylsulfonylindole-2-carboxamide (CSIC), and three rapid-equilibrium NNRTI, delavirdine (DLV) (Rescriptor), nevirapine (NVP) (Viramune), and UC84, in a variety of virucidal tests. Incubation of isolated HIV-1 virions with UC781, EFV, or CSIC rapidly inactivated the virus, whereas DLV, NVP, and UC84 were ineffective in this respect. Exposure of H9+ cells chronically infected by HIV-1 to the tight-binding NNRTI abolished the infectivity of nascent virus subsequently produced by these cells following removal of extracellular drug, thereby preventing cell-to-cell virus transmission in the absence of exogenous drug. In contrast, cell-to-cell transmission of HIV was blocked by DLV, NVP, and UC84 only when the drug remained in the extracellular medium. Pretreatment of uninfected lymphocytoid cells with UC781, EFV, or CSIC, but not DLV, NVP, or UC84, protected these cells from subsequent HIV-1 infection in the absence of extracellular drug. The protective effect was dependent on both the dose of NNRTI and the viral load. The overall virucidal efficacy of the tight-binding NNRTI tested was CSIC > UC781 approximately EFV. We conclude that the tight-binding mode of inhibition is an essential characteristic for virucidal NNRTI and that antiviral potency is an insufficient predictor for virucidal utility of NNRTI.
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PMID:A tight-binding mode of inhibition is essential for anti-human immunodeficiency virus type 1 virucidal activity of nonnucleoside reverse transcriptase inhibitors. 1201


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