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)

The enormous resources spent on developing inhibitors of the HIV proteinase is finally proving worth while. The FDA in the USA approved saquinavir (Invirase, Roche) for treatment of AIDS in December 1995, and the presumably even more useful inhibitors, ritonavir (Norvir, Abbott) and indinavir (Crixivan, Merck) in March 1996. The clinical trials indicate that these substances are more efficient antiviral agents than the well known reverse transcriptase inhibitors (e.g., AZT or ddC). In the present article, the function of the HIV proteinase will be discussed, as well as the drug design strategies leading to the success. We believe that the combination of biotechnology and computer modelling is a potent tool for designing drugs, and that these proteinase inhibitors not only signal optimism in the treatment of AIDS, but also a new era in the development of therapeutics.
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PMID:[The HIV proteinase--a target for antiviral agents]. 897 9

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

Four protease inhibitors are compared: Saquinavir (Invirase, Fortovase), Indinavir (Crixivan), Ritonavir (Norvir), and Nelfinavir (Viracept). Key questions are answered on how dosages change when combined with nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and other protease inhibitors. Information on administration and storage and the impact of each drug on disease development are reviewed. Drug interactions between protease inhibitors and other HIV drugs and non-HIV medications are described. Side effects are also discussed. Pediatric use is addressed, including suggested dosages. Contact information for each manufacturer is provided, along with approximate annual price for treatment.
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PMID:Protease inhibitors at a glance.... 1136 98

This fall, ABT-378 will be available in a limited supply through Abbott Labs= compassionate use program. ABT-378 is a new protease inhibitor that may be effective in patients who have developed a resistance to other protease inhibitors, including Fortovase and Norvir. The drug will be available to 200 to 300 people with CD4 counts below 50 who do not have other treatment options. Gilead=s newest nucleotide reverse transcriptase inhibitor, PMPA, will also be available through a compassionate use program. PMPA appears to be more powerful than adefovir, PMPA's predecessor, but the potential side effects of PMPA are unknown. Contact information is provided.
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PMID:Upcoming compassionate use programs for two new antiretrovirals will begin this fall. 1136 64

Agouron Pharmaceuticals trial results suggest additional treatment options for people taking or considering taking Viracept in combination with other anti-HIV drugs. The clinical test results with Viracept and other drugs are presented. Viracept was tested for safety and efficacy with Fortovase (saquinavir soft gel), Norvir (ritonavir), Crixivan (indinavir), 1592 (abacavir), and non-nucleoside reverse transcriptase inhibitors.
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PMID:Protease inhibitor combos. 1136 48

Efavirenz (Sustiva), Bristol-Myers Squibb) is a non-nucleoside reverse transcriptase inhibitor that has been used successfully since the late 1990s to treat HIV-1 infection, and has since become a cornerstone of antiretroviral therapy. The efficacy and potency of efavirenz has been established in many clinical trials and cohort studies, where it has been compared with unboosted or ritonavir (Norvir, Abbott Laboratories Ltd)-boosted protease inhibitors, nevirapine (Viramune, Boehringer Ingelheim Ltd); and three nucleoside analog-based regimens. Pharmacokinetics allowing for a convenient once-daily administration make efavirenz one of the first agents to be included in once-daily regimens. Tolerability of efavirenz is satisfactory, although CNS-related toxicity can occur, and is still poorly understood. New insights into the pharmacokinetics of efavirenz could help to manage this unwanted toxicity. This drug profile will examine the principal data concerning the efficacy, pharmacokinetics and safety that have made efavirenz a standard of care in HIV-1 therapy, and will comment on new data that could change the way efavirenz is used in the near future.
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PMID:Efavirenz for HIV-1 infection in adults: an overview. 1548 31

Antiretroviral treatment of HIV-infected pregnant women is widely used to prevent mother-to-child HIV transmission and as primary therapy of maternal HIV infection. The physiological changes associated with pregnancy have a large impact on drug disposition, and changes in antiretroviral pharmacokinetics during pregnancy must be understood for these drugs to be used safely and effectively in pregnant women. Zidovudine and didanosine, two of the nucleoside reverse transcriptase inhibitors, demonstrate an increase in clearance and decrease in area under the concentration-time curve during pregnancy. The clinical significance of these changes is unknown due to the lack of a clear relationship between plasma concentrations of nucleoside reverse transcriptase inhibitors and clinical effects. Pharmacokinetic parameters of lamivudine, stavudine and abacavir are not significantly changed during pregnancy. There are no data describing the effect of pregnancy on the pharmacokinetics of the other nucleoside/nucleotide analogues (zalcitabine, emtricitabine and tenofovir). Pregnancy does not appear to have a significant effect on the pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor nevirapine and there are no data describing the pharmacokinetics of the other non-nucleoside reverse transcriptase inhibitors (efavirenz and delavirdine) during pregnancy. Reduced plasma concentrations during pregnancy have been described for several of the protease inhibitors, including nelfinavir (with administration of 750 mg three times daily), indinavir, saquinavir and Kaletra (a co-formulation of lopinavir and ritonavir). Plasma concentrations equivalent to those in nonpregnant adults have been reported in pregnant women receiving nelfinavir at doses of 1250 mg twice daily, and the addition of ritonavir to saquinavir greatly increases saquinavir exposure to therapeutic concentrations in pregnant women. No pregnancy pharmacokinetic data are available for the newer protease inhibitors atazanavir and fosamprenavir, or with other dual protease inhibitor combinations that include low dose ritonavir to boost concentrations of the coadministered protease inhibitor. Further investigations of antiretroviral pharmacology during pregnancy, including protein binding studies, are urgently needed.
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PMID:Pharmacokinetics of antiretrovirals in pregnant women. 1556 88

We describe a 50-year-old Caucasian man with a family history of myoclonic epilepsy associated with ragged red fibers (MERRF) and a diagnosis of Human Immunodeficiency Virus (HIV). The patient had multiple risk factors for contracting HIV and was being followed in our clinic at the time of his diagnosis. Initial testing following seroconversion revealed a baseline CD4+ T-lymphocyte count of 652 x 10(6)cells/l and a HIV-1 RNA of 14,781 copies/ml. He reported exercise intolerance and had mild neurologic deficits, which worsened around the time of HIV seroconversion. These symptoms led to his subsequent diagnosis of MERRF by the detection of the A8344G point mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). The baseline estimated proportion of mutant genome was 39%. He showed a rapid course of HIV disease progression with a CD4+ T-lymphocyte nadir of 174 x 10(6) cells/l associated with a HIV-1 RNA of 238,178 copies/ml, within 17 months following HIV seroconversion. To avoid further mitochondrial insult, which could result from the use of a standard nucleoside reverse transcriptase inhibitor-containing regimen, a protease inhibitor regimen consisting of hard-gel saquinavir (Invirase), and lopinavir/ritonavir (Kaletra) was chosen for this patient. The patient's CD4+ T-lymphocyte count increased to 282 x 10(6)cells/l and his viral load became undetectable 7 months following the initiation of antiretroviral therapy. His neurologic symptoms did not worsen on this antiretroviral regimen. When initiating HIV therapy in individuals with metabolic myopathies related to mitochondrial dysfunction, it may be important to design an antiviral regimen that minimizes mitochondrial damage, yet effectively maintains durable viral suppression.
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PMID:HIV disease progression and limited antiretroviral treatment options for a HIV-1 infected individual with myoclonic epilepsy associated with ragged red fibers. 1612 Mar 82

Coformulated lopinavir/ritonavir (Kaletra) is a boosted protease inhibitor (PI) containing lopinavir and low-dose ritonavir. It is approved for use in combination with other antiretroviral drugs for the treatment of HIV infection in adults, adolescents and children aged >or=6 months (in the US) or >or=2 years (in the EU).Lopinavir/ritonavir-based antiretroviral therapy (ART) is generally well tolerated and has shown durable virological efficacy in clinical trials in ART-naive and -experienced patients with virological failure. Lopinavir/ritonavir is one of the preferred PIs for first-line treatment of HIV infection in adults, adolescents and children, according to US and British guidelines, reflecting its comparatively better virological efficacy than nelfinavir and low incidence of de novo resistance during long-term treatment. Lopinavir/ritonavir-based treatment may produce a more effective virological response than other PI-based regimens in single PI-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive patients. In PI- and NNRTI-experienced patients, atazanavir/saquinavir was inferior to lopinavir/ritonavir; further well designed trials are required to determine the comparative efficacy of lopinavir/ritonavir versus other PIs such as ritonavir-boosted atazanavir, or fosamprenavir or tipranavir in these patients. Lopinavir/ritonavir is more likely than atazanavir (alone or boosted) or nelfinavir to cause hypertriglyceridaemia and is associated with a higher incidence of hypercholesterolaemia than atazanavir (alone or boosted). The new lopinavir/ritonavir tablet coformulation offers a reduced pill count and lack of food interaction, and ART-naive patients in the US and Canada, who are not receiving efavirenz, nelfinavir, nevirapine or amprenavir, may benefit from convenient once-daily administration of lopinavir/ritonavir. Thus, lopinavir/ritonavir is a convenient, effective option for use in the treatment of HIV infection in ART-naive and -experienced adults, adolescents and children.
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PMID:Lopinavir/ritonavir: a review of its use in the management of HIV infection. 1682 6

We report on a patient who received a diagnosis of HIV infection following kidney transplantation some years earlier. As a result of intolerance and failure of nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI)-containing regimens, he was started on Kaletra single agent HAART. Kaletra was well tolerated and resulted in sustained viral load suppression below the limit of detection for at least 36 months.
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PMID:Kaletra single agent HAART after intolerance of NRTI- and NNRTI-containing regimens following kidney transplantation. 1756 64


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