Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Upjohn Pharmacia started an expanded access program for delavirdine (Rescriptor) for patients with CD4 cell counts below 300 who are failing other therapies and receiving at least one other antiretroviral drug. Delavirdine, a non-nucleoside reverse transcriptase inhibitor, has been found to be synergistic with other antiretrovirals such as AZT and ddI.
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PMID:Delavirdine expanded access program. 1136 51

Data on nonnucleoside reverse transcriptase inhibitors presented at the Vancouver conference is provided. Unexpectedly strong antiretroviral effects were found for 1592U89 succinate, a guanosine nucleoside analog being developed by Glaxo Wellcome. Lobucavir, another guanosine nucleoside analog, apparently has activity against most herpes viruses. Clinical trial results on the ddI/d4T combination and the ddI/delavirdine combination are presented.
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PMID:Antiviral roundup. 1136 20

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

At the 36th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC), updates on research on non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and newer treatments were presented. Among the research topics reviewed are results from the CAESAR study, guidelines for use of antiretrovirals, and the efficacy of new antiretroviral combinations. Also included are data tables showing the impact of viral load and CD4 count on risk of progression among 2,008 persons in trials of delavirdine; the detection of HIV RNA after 40 to 52 weeks in a trial of nevirapine/ZDV/ddI; viral load and CD4 changes in a phase I/II study of 141W94; viral load changes, principal side effects, and dropouts in a trial of ritonavir plus saquinavir; clinical endpoint results of the CAESAR trial; viral load and CD4 changes after 50 weeks of IL-2 plus indinavir; comparison of regimens for treating CMV retinitis; prevalence of Kaposi's sarcoma-associated herpesvirus antigen in HIV-positive and -negative groups; and rates of MAC bacteremia in ACTG 196/CPCRA 009, a trial comparing clarithromycin, rifabutin, and the combination for prophylaxis.
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PMID:Piloting the meanders of AIDS research. 1136 56

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

Results of clinical trials using delavirdine, a reverse transcriptase inhibitor, were met with mixed reactions from the FDA Antiviral Drugs Advisory Committee. Half of the committee voting on accelerated approval were not convinced that viral and CD4 results would provide a clinical benefit. Three trials combining delavirdine with AZT and ddI were conducted. Two of these trials showed reasonable increases in CD4 count; the other showed a mild increase in CD4 count, but with an increased number of deaths in the group receiving delavirdine vs. placebo. The committee used an in-depth analysis of these trials to point out confusing issues brought up by the mixed results of the trials. Controversy remains about the longer-term significance of the CD4 and viral load values. Other issues surrounding the use of delavirdine involve adverse effects, development of viral resistance, and interactions with a variety of drugs. In contrast to delavirdine, nevirapine, another reverse transcriptase inhibitor, sailed through approval with no problems, allowing observers to compare the two approval processes.
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PMID:Delavirdine data: skewed or skewered? 1136 99

While it appears that protease inhibitors in combination therapies are saving lives, questions continue: (1) which combinations of protease inhibitors and other antiretroviral agents are most effective in restoring immune function, (2) how these combinations can be used most effectively, and (3) what is the best time to start using them? An evaluation is presented on the immunological value of specific drug cocktail combinations and a comparison of the best and worst drug combinations and the reasons for this assessment. It indicates that Norvir is the most effective of all four protease inhibitors in preventing opportunistic infections, lymphomas, and cancers. D4T and 3TC are the safest and most effective of the nucleosides for preventing or remitting opportunistic infections when used with protease inhibitors. Rescriptor is the most therapeutic of the two non-nucleoside reverse transcriptase inhibitors in increasing absorption of protease inhibitors. The best drug combination therapies are listed as follows: Norvir plus Rescriptor; Norvir plus D4T; Norvir plus 3TC; Norvir, Rescriptor, and D4T; Norvir, Rescriptor, and 3TC; Norvir, D4T, and 3TC; and Crixivan or Viracept plus Rescriptor plus either D4T or 3TC. The worst drug combination therapies are listed as follows: AZT plus ddI (used in combination with a protease inhibitor); AZT or ddI or Combivir (used in combinations with a protease inhibitor); and any two protease inhibitors used together in any person with active hepatitis or elevated liver enzymes or impaired kidney function.
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PMID:An evaluation of drug cocktail combinations for their immunological value in preventing/remitting opportunistic infections. 1136 16

Hydroxyurea obstructs HIV from reproducing, is effective when combined with nucleoside analogue reverse transcriptase inhibitors, and it is difficult for HIV to develop a resistance to it. The combination of Hydroxyurea and ddI may be effective in targeting the HIV virus that hides in resting cells. This is in contrast to most other anti-HIV drugs, which tend to target HIV in activated cells. Two studies are described that echo the benefits of combining Hydroxyurea with ddI. Another study employed the previous combination with Indinavir, and all participants achieved below 400 copies of HIV RNA. Observations of three individuals, who discontinued treatments subsequent to taking regimens including Hydroxyurea, indicate that they have maintained HIV RNA below the level of detection. These case studies are not necessarily a good representation of the people actually using Hydroxyurea. More research is necessary to determine the best way to utilize this drug.
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PMID:Hydroxyurea - new observations. 1136 14


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