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)

Indinavir is a protease inhibitor used in the treatment of patients with HIV infection. Combination antiretroviral therapy with indinavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is associated with greater reductions in viral load, greater increases in CD4+ cell counts, and reduced morbidity and mortality when compared with 2 NRTIs alone. In the landmark clinical trial ACTG 320, the rate of progression to AIDS or death (primary end-point) among zidovudine-experienced patients treated with indinavir, zidovudine and lamivudine was approximately half that of patients who received only zidovudine plus lamivudine (6 vs 11%; p < 0.001). The durability of an indinavir-containing regimen was demonstrated in Merck protocol 035, an ongoing trial in which a significant proportion of patients had sustained viral suppression for up to 3 years. Merck protocol 039, also an ongoing trial, showed a greater effect on surrogate markers of HIV disease progression with indinavir-based triple therapy than with zidovudine plus lamivudine or indinavir monotherapy in patients with advanced disease (median baseline CD4+ count 15 cells/microL). Numerous additional clinical trials have established the beneficial antiviral and immunological effects of indinavir in both antiretroviral-naive and -experienced patients with HIV infection. Indinavir is associated with various drug class-related adverse events, including gastrointestinal disturbances (e.g. nausea, diarrhoea), headache and asthenia/fatigue. A lipodystrophy syndrome has been commonly reported with indinavir and other protease inhibitors combined with NRTIs, but it has also been reported in many protease inhibitor-naive patients, and a definitive causal link has not been established between the syndrome and protease inhibitors. Nephrolithiasis may develop in about 9% of patients receiving indinavir but does not appear to be associated with other protease inhibitors; <0.5% of patients receiving indinavir discontinue the drug because of nephrolithiasis, which may be the extreme end of a continuum of crystal-related renal syndromes. Additional renal problems (e.g. nephropathy) have been reported in small numbers of patients receiving indinavir. In summary, indinavir is a protease inhibitor with well documented efficacy when used as part of combined therapy in patients with HIV infection. Both US and UK treatment guidelines continue to recommend protease inhibitor-based regimens including indinavir as a first-line option. Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues. Indinavir-containing triple therapy has demonstrated positive effects not only on surrogate markers of disease progression, but also on clinical end-points of mortality and morbidity in patients with HIV disease. Protease inhibitors are a significant advance in the care of patients with HIV infection, and, in an era of evidence-based medicine, indinavir represents an important component of antiretroviral treatment strategies.
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PMID:Indinavir: a review of its use in the management of HIV infection. 1065 94

The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with > or = 12 months of nucleoside analogue monotherapy, and > or = 15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.
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PMID:Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease. 1139 23

Since limited literature exists regarding the outcomes of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) treatment in the highly active antiretroviral therapy (HAART) era, a cross-sectional survey was carried out in a population of around 1000 HIV-infected patients in a single northern Italian university hospital, to assess the frequency, background and long-term evolution of anti-HIV treatment conducted with two NRTIs. An appreciable proportion (20.4%) of the 798 HIV-infected patients currently treated with antiretrovirals at our centre still take a dual NRTI combination, and the great majority of them (68.7%) have a stable disease course (characterized by a viral load <3.7 log(10) HIV RNA copies/mL, a maintained CD4(+) lymphocyte count and absence of HIV disease progression after at least 24 months of follow-up), regardless of the selected regimen, prior antiretroviral therapy use, and baseline virological and immunological situation. Further studies are warranted to establish whether dual NRTI regimens may have residual indications in the HAART era, and whether the shift to a triple antiretroviral combination is expected to lead to long-term advantages in patients with a low risk of disease progression while on dual NRTI treatment.
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PMID:Dual nucleoside analogue treatment in the era of highly active antiretroviral therapy (HAART): a single-centre cross-sectional survey. 1148 6

In comparison with HIV infection in adults, higher HIV RNA levels in children with perinatal HIV infection, differences in the natural history of HIV disease progression, and the presence of a relatively immature immune system contribute to the more complex and problematic nature of pediatric antiretroviral therapy. Current US treatment guidelines for pediatric HIV infection advocate aggressive therapy with potent combination antiretroviral regimens, to achieve profound and durable suppression of viral replication and preservation of immune function. The combination of a protease inhibitor (PI) and dual nucleoside reverse transcriptase inhibitors (NRTIs) is the most commonly recommended form of highly active antiretroviral treatment (HAART). However, use of PI therapy in pediatrics has been constrained by the lack of suitable drug formulations, a paucity of pharmacokinetic and safety data, and drug intolerance. Pharmacokinetic studies of PIs demonstrate frequent differences between children and adults, and greater variability among children, which has led to subtherapeutic dosage regimens and the development of viral resistance. The optimal dosage of many PIs in younger children is not yet known. A therapeutically important drug interaction associated with PIs is that occurring between the various PIs themselves, which allows lower doses of PI at less frequent intervals. Dual PI regimens will probably become more common, as they permit a simpler antiretroviral regimen, lower pill/medication burden, fewer adverse effects and improved adherence. Poor adherence to antiretroviral therapy remains the greatest barrier to overall success in the treatment of HIV-infected children. The key to improving adherence in HIV-infected children is to find treatment regimens that are better suited to their normal life. With improvements in existing PIs and the development of newer ones, simplification of current antiretroviral therapy to once-daily regimens without loss of potency should be achievable. PI-containing HAART has transformed HIV infection into a chronic illness, and HIV-infected children now live longer.
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PMID:The role of protease inhibitor therapy in children with HIV infection. 1217 73

Highly active antiretroviral therapy (HAART) commonly leads to persistent dyslipidemia and insulin resistance that appear likely to confer an increased incidence of cardiovascular disease (CVD). Both protease inhibitors (PIs) and, to a lesser extent, nucleoside analog reverse transcriptase inhibitors (NRTIs) appear to be involved, through direct metabolic effects of PIs and an indirect effect of PI and NRTI-related lipodystrophy. Several studies have found a variable relationship between CVD incidence and HAART, but these studies were not prospective and may not have been adequately powered. A variety of treatment strategies have been evaluated for dyslipidemia and insulin resistance, including lifestyle changes, drugs, and antiretroviral switching, but their relative safety, efficacy and roles are unclear. Although treatment of dyslipidemia and insulin resistance is commonly recommended, it should be remembered that such therapy is likely to be of greater benefit in those with a greater perceived CVD risk (i.e., multiple risk factors) and the lowest risk of HIV disease progression.
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PMID:Cardiovascular risk factors in HIV-infected patients. 1456 61

The clinical goals of HIV treatment are optimally accomplished through consistent high-level adherence to highly active antiretroviral therapy (HAART) and durable suppression of the viral load. However, as a result of the need for lifelong therapy and HIV's prodigious replication rate and error-prone reverse transcriptase, varying amounts of antiretroviral drug resistance are common in treated individuals. Medication adherence is linked to the development of drug resistance, although not by a simple linear relationship. Recent studies have suggested that extensive drug resistance is not a major determinant of HIV disease progression and death. Rather, failure to access care and discontinuation of or non-adherence with therapy are arguably the most important factors associated with HIV disease progression in the HAART era. Other data indicate that continued therapy in the setting of extensive drug resistance and the inability to achieve viral suppression can provide continued clinical benefit. Such benefit may be mediated, at least partially, by reductions in viral fitness associated with drug resistance mutations.
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PMID:Antiretroviral adherence, drug resistance, viral fitness and HIV disease progression: a tangled web is woven. 1572 89

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

The use of highly active antiretroviral therapy (HAART) has significantly slowed the HIV disease progression. However, adverse effects are now a limiting cause of HAART benefit in a substantial proportion of patients. Particularly hepatotoxicity which is a common complication occurring during every HAART regimen. All antiretroviral (ARV) drugs classes, Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTI), non-Nucleoside reverse transcriptase inhibitors (nNRTI) and Protease Inhibitors (PI) may cause hepatotoxicity but in different pathways. Many risk factors have been identified for developing antiretroviral-related hepatotoxicity, however severe hepatitis remains very uncommon in patients receiving HAART, also if the incidence of hepatotoxicity is rather high. That being the case, means that every new available antiretroviral drug strongly necessities studies which can evaluate its hepatotoxicity and drug-drug interactions, to define the potential risk factors and the outcome of any side effects. This report will review the risk factors, the epidemiology and the pathogenic mechanisms of hepatotoxicity caused in every antiretroviral drug.
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PMID:Hepatotoxicity of antiretroviral drugs. 1630 5

The purpose of the review was to explore the effects of nutritional supplements in children with HIV/AIDS. Nutritional supplements were found to have both positive and negative effects in HIV/ AIDS children. It was found that selenium helps to boost immunity. Vitamin D supplementation was found to delay mother to child transmission (MTCT) of HIV and to reduce stunted growth associated with persistent diarrhea. Vitamins B, C, and E were found to delay HIV disease progression, reduce oxidative stress and HIV viral load. Multivitamin supplementation was found to be more effective in delaying HIV disease progression. Protein nutrition was found to improve cognitive and motor developments of children as well as helping HIV-positive children achieve 100% weight for height. Some nutrient supplements, however, were found to have negative effects on HIV/AIDS children. Vitamin A was found to double the risk of mortality of HIV/AIDS in infants exposed to HIV via breastfeeding. Zinc was found to have a positive effect on production of infectious virus through its action on reverse transcriptase. Some micronutrional interact with each other leading to harmful side effects such as diarrhea. Some nutritional supplements interact with antiretroviral drugs leading to treatment failure. It is important for children to be given right doses of nutritional supplements and that their immune system should be closely monitored.
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PMID:Effects of nutritional supplementation on children with HIV/AIDS in China. 2256 1

The role of HIV-1-specific antibody responses in HIV disease progression is complex and would benefit from analysis techniques that examine clusterings of responses. Protein microarray platforms facilitate the simultaneous evaluation of numerous protein-specific antibody responses, though excessive data are cumbersome in analyses. Principal components analysis (PCA) reduces data dimensionality by generating fewer composite variables that maximally account for variance in a dataset. To identify clusters of antibody responses involved in disease control, we investigated the association of HIV-1-specific antibody responses by protein microarray, and assessed their association with disease progression using PCA in a nested cohort design. Associations observed among collections of antibody responses paralleled protein-specific responses. At baseline, greater antibody responses to the transmembrane glycoprotein (TM) and reverse transcriptase (RT) were associated with higher viral loads, while responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and integrase (IN) proteins were associated with lower viral loads. Over 12 months greater antibody responses were associated with smaller decreases in CD4 count (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and protein microarray analyses highlighted a collection of HIV-specific antibody responses that together were associated with reduced disease progression, and may not have been identified by examining individual antibody responses. This technique may be useful to explore multifaceted host-disease interactions, such as HIV coinfections.
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PMID:Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression. 2413 21


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