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)

The debate of monotherapy vs. combination therapy during the July 25th-27th Consensus Symposium on Combined Antiviral Therapy is discussed. Specific topics addressed at the Lisbon conference included whether the protease inhibitor, indinavir, could antagonize the effects of ZDV plus 3TC; synergy claimed with VX-478 and ZDV, ddI, and other reverse transcriptase inhibitors; a proposal that ablative therapy against HIV during the first weeks of infection could become a reasonable tactic when patients are diagnosed very early; a discussion of recent data suggesting that cross-resistance of HIV to several protease inhibitors is not an insurmountable problem and that convergent therapy with the drugs remains a possibility; and indications that HIV doubly resistant to 3TC and ZDV can emerge, at least when 3TC is started first and ZDV is added later.
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PMID:A Lisbon traviata. Are clinicians ready to sing addio to monotherapy and libiamo to combinations? 1136 92

In an interview, Dr. Charles A. B. Boucher responds to questions about double resistance to 3TC and ZDV, the effects of mutations on reverse transcriptase inhibitors, viral load and prospects for individualized therapy, combination drug therapy issues, and cross resistance to protease inhibitors. Final comments address the confusion about when aggressive HIV drug therapy should begin, and the problem of HIV drug resistance.
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PMID:An interview with Charles A.B. Boucher, MD, PhD. Interview by Mark Mascolini. 1136 72

A clinical trial, protocol ICC-002, is comparing three anti-HIV treatment regimens: 1) AZT and ddI; 2) AZT, ddI, and 3TC; and 3) AZT, ddI, and nevirapine (an experimental non-nucleoside reverse transcriptase inhibitor). The Inter-Company Collaboration for AIDS Drug Development will enroll 225 participants with CD4 counts between 200 and 500, who have not previously used antiretrovirals. The study will compare the effects of these treatments on viral load, CD4 count, and other disease progression markers.
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PMID:New double vs. triple antiviral combination study, CD4 200-500, no prior treatment. 1136 52

Results of ACTG 175 and Delta, large multicenter studies comparing combinations of nucleoside antiretroviral drugs with monotherapy, are reported. ACTG 175 enrolled 2,500 HIV-infected patients (1,000 subjects were AZT naive) over a 3-year period and randomized them to one of four drug regimens: AZT plus ddC, AZT plus ddI, AZT alone, or ddI alone. In moderately immunocompromised patients, the best results are obtained with either combination, or with ddI alone. In patients already on AZT, it is better to add or switch to ddI than to continue AZT monotherapy. The Delta trial enrolled 3,300 subjects and studied the same combinations as in ACTG 175 and AZT monotherapy, but did not study ddI monotherapy. Patients receiving combination therapy did better than those receiving AZT alone. AZT-experienced patients, regardless of the treatment received, experienced similar rates of progression to AIDS or death. This study was ceased prematurely due to the high rate of deaths in AZT-naive subjects receiving AZT alone compared to combination therapies. Other drug combination studies, such as AZT combined with 3TC, show superiority to AZT monotherapy in decreasing viral load and increasing CD4 counts, but do not correlate the results with clinical benefit. Other issues discussed include development and use of non-nucleoside reverse transcriptase inhibitors, studies involving HIV protease inhibitors, and the development of resistance and cross-resistance to various classes of antiviral agents.
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PMID:Antiretroviral combination treatment prolongs life in people with HIV/AIDS. 1136 17

Information about protease inhibitors and other antiretroviral drugs used to treat AIDS-related opportunistic infections is provided. Specific drugs addressed include ritonavir, a protease inhibitor that received the fastest approval in history, for HIV infection; Vitrasert, an intraocular form of ganciclovir, for treating CMV retinitis; 3TC, an antiviral agent for treating HIV infection; a combination of saquinavir and ritonavir for treating HIV infection; nevirapine, a reverse transcriptase inhibitor for HIV infection; nitazoxanide, available through an FDA-approved expanded access program, for cryptosporidiosis; indinavir, an HIV protease inhibitor used for HIV infection; and a combination of ddC and AZT for HIV infection.
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PMID:[New treatments for HIV]. 1136 30

A comparison chart of antiviral drug combinations provides information and the initial data on various anti-HIV combinations using nine possible drugs, including AZT, saquinavir, 3TC, ddC, ddI, d4T, and nevirapine. The chart compares the results of various combinations of reverse transcriptase inhibitors and protease inhibitors. None of the drugs have been studied with large cohorts of people or over a long enough period of time to provide scientifically accurate conclusions.
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PMID:Re: the combination antiretroviral chart. 1136 14

Nevirapine, the ninth approved anti-HIV drug, is the first of a new class of pharmaceuticals developed for HIV treatment. A non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine targets the same HIV enzyme as AZT, ddI, ddC, d4T and 3TC. A three-drug treatment including AZT and ddI was shown to be significantly better than an AZT/ddI combination in patients who had received no prior treatment. The drug has a long half-life, which means that it can be administered less often.
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PMID:Nevirapine approved by FDA. Food and Drug Administration. 1136 18

Various drugs used in HIV therapy, along with their synonyms, are given. Drugs are listed by their action and include reverse transcriptase inhibitors, protease inhibitors, and hydroxyurea. Hydroxyurea was originally developed as an oncology drug but may work in a unique manner against HIV. Common or important side effects are given for each entry. Specific drugs are as follows: AZT, ddI, ddC, d4T, 3TC, nevirapine, delavirdine, indinavir, ritonavir, saquinavir, and nelfinavir.
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PMID:The new antiretroviral arsenal. 1136 1

Reports from the 1997 Fourth Conference on Human Retroviruses and Opportunistic Infections continued to present the success of three-drug combinations for the treatment of HIV, and some studies indicate enough restoration of the immune system to sufficiently overcome some opportunistic infections. Updates are provided on previously-reported studies as well as those involving new drugs and combinations, including therapies for advanced disease. Results indicate that 3TC should only be used as part of a three-drug combination. Other reports show that people who start protease inhibitor therapy with low CD4+ cell counts (fewer than 100 cells) and get good CD4+ cell responses are still at risk of developing opportunistic infections, but it is advised that they should continue to take their prophylaxis therapies. Finally, preliminary results indicate that the new generation of nucleoside analogues, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors offer a significant advantage over the current generation of drugs. This will allow new therapies and new combination options for people who have already used or are intolerant to the currently available therapies.
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PMID:Antiviral update. 1136 16

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


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