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)

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