Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amprenavir (Agenerase, 141-W94, VX-478) is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PRI) recently approved for the treatment of HIV-1 infection in the United States. A major cause of treatment failure is the development of resistance to PRIs. One potential use for amprenavir is as salvage therapy for patients for whom treatment that includes one (or more) of the other four currently approved PRIs-saquinavir, indinavir, ritonavir, and nelfinavir-has failed. We evaluated the cross-resistance to amprenavir of viruses that evolved during treatment with the two most commonly prescribed PRIs, nelfinavir and indinavir. Unexpectedly, a dramatic increase in susceptibility (2.5- to 12. 5-fold) was observed with 20 of 312 (6.4%) patient viruses analyzed. The most pronounced increases in susceptibility were strongly associated with an N88S mutation in protease. All viruses that carried the N88S mutation were hypersensitive to amprenavir. Site-directed mutagenesis studies confirmed the causal role of N88S in determining amprenavir hypersensitivity. The presence of the N88S mutation and associated amprenavir hypersensitivity may be useful in predicting an improved clinical response to amprenavir salvage therapy.
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PMID:A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. 1075 56

More antiretroviral drugs are becoming available, increasing potential treatment regimens but also increasing the complexity of HIV treatment. The 4 newest of the 15 available antiretroviral agents are described: efavirenz (Sustiva, EFV), abacavir (Ziagen, ABC), adefovir (Preveon, ADV), and amprenavir (Agenerase, APV). Information on dosing, side effects, and interactions with other drugs is provided.
Hopkins HIV Rep 1999 Jan
PMID:The new drugs and how to use them. 1136 60

New anti-HIV drugs that are expected to become available in the future are discussed. The potent protease inhibitor amprenavir (Agenerase) is expected to be available in pharmacies by early 1999. Results of a study of treatment-naive, HIV-positive people showed that those taking amprenavir as part of a three-drug combination therapy, with AZT and 3TC, had better viral reduction than those using AZT and 3TC alone. In a French study of the non-nucleoside reverse transcriptase inhibitor Nevirapine, and a similar study of Delavirdine, a majority of participants had HIV RNA levels below the limit of detection. Further comparative studies are needed between Nevirapine, Delavirdine and the more costly, highly publicized competitor, efavirenz. Several studies of regimens that include protease inhibitors compare dosing twice daily to three times a day. A Canadian study describes salvage therapies, for people who have failed previous treatment with protease inhibitors, that can include up to nine drugs. Because there is a shortage in the development of new types of HIV drugs, people are encouraged to carefully consider when to begin treatment and what medical options are available.
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PMID:Antivirals update. 1136 1

The Food and Drug Administration (FDA) has approved amprenavir (Agenerase, formerly known as 141W94 and VX-478) for treatment of HIV. The drug is a second-generation protease inhibitor, discovered by Vertex Pharmaceuticals and marketed by Glaxo Wellcome. The amprenavir regimen consists of eight capsules twice daily, with or without food. There is also a liquid formulation for pediatric use. Clinical studies show amprenavir to be a potent HIV inhibitor, that can penetrate the blood-brain barrier. Persons taking hormonal contraceptives or rifabutin will need to adjust the dose, while persons with sulfa allergies may have difficulty taking the drug. Several drugs including Astemizole (Hismanal) cannot be taken with amprenavir.
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PMID:Amprenavir (Agenerase) receives FDA approval. Food and Drug Administration. 1136 93

Amprenavir (Agenerase) received accelerated approval from the Food and Drug Administration (FDA) in April 1999. The protease inhibitor, developed by Vertex Pharmaceuticals and marketed by Glaxo Wellcome, is the 16th approved drug for HIV treatment. The capsules are taken twice daily, with or without food. Side effects and potential drug interactions are listed. Cross-resistance information is provided, along with data from earlier trials to demonstrate the drug's effectiveness against HIV. Contact information for Glaxo's patient assistance program is provided.
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PMID:Amprenavir (Agenerase). 1136 26

Protease inhibitors are the most well-known type of HIV drug, and five of them are currently approved by the Federal government. This first-generation of protease inhibitors includes Crixivan, Norvir, Fortovase, Viracept, and Agenerase. These drugs, while effective, do not eliminate HIV from the body, nor do they work well for everyone. A second-generation of protease inhibitors is in development, that researchers hope will be easier to take, and better at eliminating HIV. Included in this group are L-756,423, Tipranavir, BMS232632, and ABT-378(r). The benefits and potential drawbacks of each drug are briefly described. People who are considering switching treatments should consult their doctors about the possibility of entering a clinical trial.
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PMID:The younger generation. 1136 65

The new, second-generation protease inhibitor, amprenavir (Agenerase), discovered by Vertex Pharmaceuticals and clinically developed by Glaxo Wellcome, is awaiting regulatory approval in the U.S. and Europe. Amprenavir has been given "fast track" status by the U.S. Food and Drug Administration (FDA). Amprenavir has shown promising results in human testing, and seems to be a potent inhibitor of HIV replication. Researchers found amprenavir to be successful when used in a three-drug combination with AZT and 3TC. Other data show the drug to be synergistic with abacavir, and to have less cross-resistance than other drugs in the class. Study details, side effects, and drug interactions are described. Contact information for Glaxo Wellcome's expanded access program are also provided.
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PMID:Amprenavir: a new protease inhibitor nears approval. 1136 44

The U.S. Food and Drug Administration has granted marketing authorization to Vertex Pharmaceuticals for Agenerase. Agenerase is the fifth drug targeting HIV's protease enzyme that has been approved to treat AIDS. It is only taken twice a day, as opposed to other approved protease drugs which are taken three times a day. However, patients will take eight Agenerase pills at each sitting, rather than two to six pills for other protease drugs.
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PMID:FDA approves an AIDS drug from Vertex. Food and Drug Administration. 1136 45

Starting from the chemical structure of the recent FDA-approved anti-HIV drug Amprenavir (Agenerase), a potent HIV-protease inhibitor, we have designed new series of Amprenavir bioisoteres in which the methylene group of the benzyl group was replaced by a sulfur atom. This structural modification has required an original multistep synthesis. Unfortunately, introduction of the sulfur atom abolished or drastically decreased both inhibitory activity on recombinant HIV protease and HIV infection protection on MT4 cell cultures.
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PMID:Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres. 1210 15

This study compared the plasma amprenavir pharmacokinetics of the human immunodeficiency virus (HIV) protease inhibitors amprenavir (Agenerase) 1,200 mg twice daily (BID) and the amprenavir prodrug GW433908, a formulation that substantially reduces the number of tablets per dose compared with amprenavir, at doses of 1,395 mg and 1,860 mg BID, in combination with abacavir 300 mg BID and lamivudine 150 mg BID in patients with HIV infection. Overall, 78 patients received study treatment. Compared with amprenavir 1,200 mg BID, both GW433908 1,395 mg BID and GW433908 1,860 mg BID delivered equivalent steady-state (ss) values for area under the plasma amprenavir concentration-time curve (AUC) at the end of a dosing interval (tau), lower maximum plasma amprenavir concentrations (30% lower), and higher plasma amprenavir concentrations at the end of a dosing interval (28% higher for GW433908 1,395 mg BID and 46% higher for GW433908 1,860 mg BID). Time-variant plasma amprenavir pharmacokinetics were observed with reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the decrease in plasma amprenavir AUC(tau,ss) versus the AUC from 0 h to infinity was 27% for GW43308 1,395 mg, 45% for GW433908 1,860 mg, and 23% for amprenavir 1,200 mg. All three regimens reduced plasma HIV-1 RNA ( approximately 2 log(10) copies/ml) and increased CD4(+) cell counts ( approximately 100 cells/mm(3)) over the initial 28 days. Adverse event profiles were consistent with those previously reported for amprenavir. Although not statistically tested, the GW433908 groups appeared to have fewer gastrointestinal symptoms. In conclusion, the protease inhibitor GW433908 delivered comparable plasma amprenavir concentrations to those delivered by amprenavir 1,200 mg BID. GW433908, in combination with abacavir and lamivudine, demonstrated potent antiviral activity and was generally well tolerated over a 4-week period.
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PMID:Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. 1469 28


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