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 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

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

The proper implementation of combination antiretroviral treatment regimens is fundamental to successful therapeutic outcomes for patients with HIV/AIDS. Unfortunately, some patients are still being prescribed contraindicated antiretroviral regimens that include: 1. stavudine plus zidovudine; 2. Invirase plus two nucleoside analog reverse transcriptase inhibitors (NRTIS); 3. zalcitabine plus didanosine; 4. zalcitabine plus stavudine; and, 5. zalcitabine plus lamivudine. Inappropriate regimens such as these either have limited effectiveness or potential severe toxicity.
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PMID:Contraindicated antiretroviral drug combinations. 1455 2

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