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)

Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear.
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PMID:Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. 1133 79

DMP 266, a nonnucleoside reverse transcriptase inhibitor, has been effective as a monotherapeutic agent in reducing viral load. How long it remains effective is unknown, and resistance development is a problem. Two trials testing combinations with DMP 266 are beginning. One test using DMP 266 with indinavir is already considered flawed because indinavir is provided as a monotherapy first. Indinavir monotherapy is believed to help HIV resistance to evolve, especially in people with high baseline viral loads. Participants who are on the monotherapy risk not receiving the full benefit from indinavir and other protease inhibitors because they trigger similar resistance mutations.
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PMID:DMP 266: keep the drug but dump the trial? 1136 85

As combination therapy for treating HIV/AIDS grows, data on how these drugs interact becomes necessary and more complex. Information is provided on drug interactions using nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors, NNRTIs and nucleoside reverse transcriptase inhibitors, DMP 266 and indinavir, AZT and delavirdine, and ritonavir and saquinavir. New concerns for some combinations have arisen concerning AZT with d4T and nevirapine with indinavir. Trial results and questions about using these drugs are provided.
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PMID:Antiviral update. 1136 72

Dupont Merck announced that its experimental non-nucleoside reverse transcriptase inhibitor DMP 266 has shown viral load reductions to undetectable levels in eighty percent of study subjects. CD4 counts also increased among the study group. Other studies are underway to study DMP 266 at higher dosages and in combination with other drugs. Enrollment information is included.
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PMID:DMP 266 study opens at Jefferson. 1136 40

DMP 266, a non-nucleoside reverse transcriptase inhibitor (NNRTI) in the same general class as nevirapine or delavirdine, is undergoing clinical trials. Potential advantages of DMP 266 are that it is only taken once a day (making adherence easier for patients), there does not appear to be serious supply problems, and drug resistance appears to develop more slowly than other NNRTIs. Two Phase II trials, DMP 266-20 and DMP 266-006, are now recruiting protease inhibitor-naive persons. The company has decided to offer the drug to volunteers who complete either trial (each lasts 24 weeks) and wish to continue. Details about both trials and contact information are provided.
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PMID:DMP 266 trials recruiting, many cities -- protease inhibitor naive. 1136 23

DuPont Merck is conducting clinical trials of its new non-nucleoside reverse transcriptase inhibitor, DMP 266, at more than 100 hospitals. The drug is the first anti-HIV medication to be taken only once a day, and it shows significant viral load decreases when taken in combination with indinavir. Side effects include rash, sinusitis, upper respiratory infection, and diarrhea. Enrollment information is included. Merck will announce an expanded access program in September 1997.
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PMID:DMP 266 on the horizon. 1136 36

Results of a 48-week phase II trial of efavirenz (SUSTIVA, formerly DMP 266) in combination with indinavir resulted in an average viral load reduction of 2.38 out of a possible 2.49 logs. A comparison group, receiving only indinavir for 48 weeks, had a 1.89 log average reduction out of a possible 2.42 logs. Efavirenz, produced by DuPont Merck, is a non-nucleoside reverse transcriptase inhibitor that is effective against many HIV variants and resistance also develops slowly. Data from another study on efavirenz will be reported at the Sixth European Conference on Clinical Aspects and Treatment of HIV Infection, October 11-15 in Hamburg, Germany. The additional number that is used to report viral load measurements is explained.
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PMID:Efavirenz (SUSTIVA, formerly DMP-266) 48-week data announced. 1136 90

DuPont Merck and Gilead Sciences are finalizing a program to make their new, experimental anti-HIV drugs available free to people who are not benefiting from other treatments. Enrollment information is included. The program includes the drugs DMP-266 and adefovir dipivoxil, and is a model for how drug companies can work together effectively to make experimental treatments available through expanded access programs. Initially, DMP-266 enrollment will be limited to 2,000 people with CD4 counts below 50 who are failing their current regimen. Adefovir will be available to 1,000 patients with CD4 counts below 50 and viral loads above 30,000. DMP-266 is a non-nucleoside reverse transcriptase inhibitor that is only taken once a day and shows great promise when used in combination with indinavir. Adefovir belongs to the nucleotide analog reverse transcriptase inhibitor class, and shows a unique resistance profile. It is also taken only once a day.
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PMID:DMP-266 and adefovir dipivoxil: 2 new AIDS drugs available to patients without treatment options. 1136 9

DuPont Merck's non-nucleoside reverse transcriptase inhibitor DMP 266 (called Sustiva or efavirenz) will be available through an expanded access program starting in October 1997. A filing for Food and Drug Administration (FDA) marketing approval is expected in March 1998. Volunteers must have CD4 counts lower than 50 in the last 3 months and be failing current treatment regimens. DMP 266 has shown effectiveness in viral suppression when combined with indinavir. Two new trials are currently enrolling for combination therapy using DMP 266 with AZT/3TC. Contact information is provided for further details.
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PMID:DMP 266 now available. 1136 51

DuPont Merck is opening an expanded access program for efavirenz (Sustiva), a non-nucleoside reverse transcriptase inhibitor (NNRTI). Efavirenz (formerly called DMP-266), the most potent NNRTI to date, is taken only once a day. To participate, patients must be failing therapy or be intolerant of current therapy. The patients are required to take the drug with another anti-HIV drug that they have never taken. Contact information for efavirenz studies, including a pediatric trial, is provided.
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PMID:DMP 266 (Sustiva) expanded access. 1136 50


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