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)

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

Gilead Sciences will offer an expanded access program for its anti-HIV agent, adefovir (Preveon). Prospective enrollees must have CD4 counts less than 50, a viral load of over 30,000 copies/ml by PCR within the past 2 months, and failed at least two nucleoside analogs and one protease inhibitor. Because adefovir has extremely modest activity, it can only function as an adjunct to other potent drug combinations. There is concern that the eligibility requirements will be problematic. DuPont Merck's non-nucleoside reverse transcriptase inhibitor Sustiva is undergoing participant registration for its expanded access program. Participants must have CD4 counts less than 50 but may have any viral load level. Glaxo's expanded access program for abacavir (1592U89) is an open-label trial with eligibility being CD4 counts less than 100. Glaxo has also opened an expanded access program for patients with moderate to severe AIDS dementia.
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PMID:Three drugs now in expanded access. 1136 20

Adefovir dipivoxil (Preveon), a nucleotide analog and a prodrug of PMEA, has been approved for a limited expanded access program for patients who have failed approved treatments. Earlier results from phase I/II trials reveal Preveon has modest anti-HIV activity. Preveon is active against virus that has developed resistance to AZT, 3TC, and other approved nucleoside analogs. To be eligible, patients must be at least 13 years old, failed at least two nucleoside analog reverse transcriptase inhibitors and one protease inhibitor, and within the last 2 months have had a CD4 count of 50 or less and a viral load of at least 30,000 by PCR or at least 15,000 by bDNA. The program will supply only Preveon and the L-carnitine. The AIDS community has expressed concerns about the drug's potential kidney toxicity with long-term use, a condition that becomes clinically evident usually after the first 4 months, possibly leading physicians into complacency in performing regular laboratory tests after that time. The study requires monthly urine testing, including serum creatinine, urine protein, and urine glucose. Another concern is the study's CD4 and viral load restrictions; AIDS advocates believe the restrictions do not allow physicians flexibility in their drug treatment decision-making.
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PMID:Adefovir dipivoxil (Preveon) expanded access begins. 1136 18

Sustiva (DMP 266 or efavirenz) has been available on an expanded access program since October 1. Sustiva is a non-nucleoside reverse transcriptase inhibitor, has fewer side effects than other drugs of its class, and is taken once a day at bedtime. Criteria for the program are T4 counts under 50 in patients whose current therapy is not working. Adefovir dipivoxil (bis-POM PMEA or Preveon) is a nucleotide analog that is also available through an expanded access program. Adefovir's properties make it less vulnerable to resistance. It is not as potent as other drugs of the same class; however, its effect seems to last longer. It is also effective against some herpesviruses and hepatitis B. Contact information is provided for both programs.
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PMID:Expanded access programs. 1136 31

The 38th Interscience Conference on Antimicrobial Agents and Chemotherapy featured information on new antiretroviral treatments, changes in dosing, and new vaccine information. Adefovir dipivoxil (Preveon) is a new nucleoside reverse transcriptase inhibitor that is administered once daily. A study of adefovir dipivoxil is described and the side effects are detailed. A clinical trial of the protease inhibitor Nelfinavir (Viracept) has shown that dosing twice a day may be as effective as the currently prescribed three times a day. Since lower dosing tends to increase a patient's adherence to treatment, it may have a long-term positive effect on treating HIV. Other drug treatments and possible changes in dosing are presented. A pneumococcal vaccine study is described, and it was found that the vaccine did not lead to an increase in viral load. Immunization against Pneumococcus is suggested for all adults who are HIV-infected.
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PMID:Antimicrobial agents and chemotherapy: highlights of the 38th Interscience Conference. 1136 34

A table charts the various nomenclature of drugs used to treat HIV and AIDS. The common name, generic name, and brand name are given for several categories including NARTIs (NRTIs, "Nukes", Nucleoside analogue reverse transcriptase inhibitors), NNRTIs (Non-nucleoside reverse transcriptase inhibitors), and PIs (Protease Inhibitors). Other drugs listed are Hydroxyurea (anti-cancer drug) and preveon (Adefovir (Nucleotide)).
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PMID:What's in a name? 1136 57

Attendees at the Second International Workshop on Salvage Therapy heard little to make them optimistic about the immediate future of salvage therapy. Treatment veterans with only a few virologic failures stand a slim chance of ongoing viral control. Current salvage treatment, even combination therapy, only pushes viral loads to below 500 copies in 20 to 40 percent of patients, and those patients who have had viral loads suppressed to below 20 copies/mL stand the best chance of having a sustained response to the treatment. Results of several studies are reviewed. Adefovir, which had been considered an option, has performed poorly in trials. One table shows the effects of nonnucleoside reverse transcriptase inhibitor/protease inhibitor (NNRTI/PI) salvage therapy in the NNRTI-naive patient. Another table presents figures to show that salvage success correlates significantly with lower viral loads prior to treatment. A third table shows the "megasalvage" track record, while a fourth presents a proposal for a rapid-assessment salvage study. The concept of using drug holidays as a means to force the immune system to begin fighting HIV on its own remains controversial.
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PMID:Salvage solitaire (or, HAART takes a holiday). 1136 32

A Food and Drug Administration (FDA) advisory panel recommended against accelerated approval for adefovir dipivoxil (Preveon). The drug belongs to a new class of drugs, nucleotide reverse transcriptase inhibitors, and was developed by Gilead Sciences as a salvage treatment for people who do not experience adequate viral suppression under other therapies. The unexpected denial was due to safety concerns; in a pivotal study, several patients who took adefovir experienced kidney failure and had to be treated with dialysis. The ramifications of the FDA's decision are not known. About 9,000 people have taken the drug through expanded access programs, and adefovir has also displayed antiviral activity against hepatitis B infections. Gilead is developing another drug, tenofovir DF, which appears more effective against HIV, with fewer side effects.
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PMID:FDA panel fails to recommend adefovir approval. Food and Drug Administration. 1136 49

Chronic hepatitis B virus (HBV) infection imposes an enormous public health burden. In patients with chronic hepatitis and high levels of viral replication, inhibitors of the virus polymerase can reduce serum titre and favourably affect the inflammatory process in the liver. Lamivudine, a reverse transcriptase inhibitor, is the first nucleoside analogue to be licensed for treatment of chronic HBV infection. Treatment effects a rapid and profound decrease of serum virus titre, with attendant clinical benefit. Unfortunately drug-resistant species may emerge after 6 months of suppressive therapy. Lamivudine-resistant species have specific amino acid substitutions in the HBV-encoded polymerase. Emergence of these species is frequently associated with loss of clinical benefit. Published data suggest that lamivudine-resistant species exhibit cross-resistance to famciclovir, thereby limiting the potential use of famciclovir with lamivudine as combination therapy. Adefovir is under clinical evaluation for treatment of wild-type and lamivudine-resistant HBV. Preliminary data suggest that adefovir achieves potent inhibition of both species. Studies of drug resistance have followed hot-on-the-heels of the development of potent antiviral therapy for chronic HBV.
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PMID:Hepatitis B virus infection: resistance to antiviral agents. 1139 60

An antisense oligodeoxynucleotide against the human immunodeficiency virus type 1 (HIV-1) Rev response element, a ribozyme complementary to the HIV-1 5'-LTR, and the reverse transcriptase inhibitors 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-adenine (PMPA) inhibited virus replication in monocyte-derived macrophages more effectively when delivered in pH-sensitive liposomes compared to the free drugs.
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PMID:Enhanced inhibition of HIV-1 replication in macrophages by antisense oligonucleotides, ribozymes and acyclic nucleoside phosphonate analogs delivered in pH-sensitive liposomes. 1156 68


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