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)

This report describes a 47-year-old woman with human immunodeficiency virus (HIV) and end-stage renal disease on hemodialysis, treated with combination antiretroviral drug therapy, who developed an acute, severe type B lactic acidosis 24 hours after homograft root replacement for endocarditis. She fully recovered after HIV medication was discontinued, along with administration of riboflavin and supportive measures including hemodialysis. The timing of this complication and previous reports suggest that open heart surgery may be a risk factor for nonischemic (type B) lactic acidosis in patients taking nucleoside analogue reverse transcriptase inhibitors.
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PMID:Type B lactic acidosis: a rare complication of antiretroviral therapy after cardiac surgery. 1240 Jul 87

Data on the efficacy and tolerability of antiretrovirals in children are limited as, in contrast to adult studies, large paediatric cohort studies are lacking. Thus, data pertaining to adults are often extrapolated to children despite the acknowledgement that children are not little adults. This review summarises information gathered from existing reports and focuses on the tolerabilities of antiretrovirals in children infected with HIV-1. The efficacy of antiretrovirals is not included in the scope of the discussion. Taste of antiretrovirals should be an important factor when considering the tolerability of antiretrovirals in children. However, antiretroviral options are often limited in young children as only some of the antiretrovirals are available as paediatric formulations. All antiretrovirals have been associated with toxicities in children, but in general, they are relatively well tolerated. The gastrointestinal system including hepatic system is most prone to being affected by these drugs. Skin rashes and hypersensitivity reactions are also associated with antiretroviral use, particularly with the non-nucleoside reverse transcriptase inhibitors. Mitochondrial toxicities that lead to impairment of liver function, pancreatic function and lactic acidosis are associated with most of the nucleoside analogues. Haematological toxicity is often a dose limiting adverse effect especially of the nucleoside analogues, in particular zidovudine. The protease inhibitors are associated with gastrointestinal intolerance (diarrhoea) and metabolic derangements that can lead to hypercholesterolaemia and hypertriglyceridaemia, which in turn and can lead to changes in body habitus. The renal system is also affected by several drugs, the most important of which is indinavir, which has been associated with renal stones and damage to the renal tubules. Fortunately, with lower incidence of major toxicity and with the range of drugs now available for paediatric use, toxicities are usually not a barrier to effect antiretroviral therapy in children.
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PMID:Tolerabilities of antiretrovirals in paediatric HIV infection. 1240 30

Nucleoside analog reverse transcriptase inhibitors (NRTI) have been used to treat HIV-infected patients for >10 years. Some severe adverse events have been attributed to mitochondrial dysfunction. Since 1991, cases of severe lactic acidosis have been reported in association with nucleoside therapy. Our objective was to report two cases of metabolic acidosis and hepatic steatosis in patients receiving stavudine (d4T) and to review the literature. A male and a female, 47 and 45 years of age, respectively, presented with abdominal pain, nausea, vomiting, and weakness after 9 and 6 months, respectively, of treatment with stavudine. At presentation, both patients had severe metabolic acidosis and liver failure. Ultrasonography showed hepatic steatosis (confirmed by biopsy in one case). All antiretroviral drugs were withdrawn and patients were treated with bicarbonate. Both patients developed fulminant liver dysfunction and multiple organ failure. We reviewed the literature and found 75 cases of lactic acidosis and hepatic steatosis associated with use of NRTI; 57 of these patients received d4T (76%). Of all cases reported in association with nucleoside therapy, 63% were females and mortality was 47%. General weakness, hepatic enzyme elevation, and liver steatosis are data that should alert physicians to this serious adverse event and to respond with prompt interruption of antiretroviral drugs and measurement of lactic acid in plasma. It is important to report serious adverse events in commercially released drugs to know prevalence in an exposed population. Physicians should be aware of risk and early signs of this serious adverse event.
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PMID:Metabolic acidosis and hepatic steatosis in two HIV-infected patients on stavudine (d4T) treatment. 1260 78

Lactic acidosis in patients infected with the human immunodeficiency virus was initially identified as a rare complication of therapy with nucleoside analog reverse transcriptase inhibitors (NRTIs). The only patient group that appears to be at greater risk is pregnant women. More recently, milder elevations in lactate (i.e., lactic acidemia or hyperlactatemia) have been found to be more common and to be associated with numerous illnesses. Mild asymptomatic lactic acidemia is common, but it appears to lead to more severe illness only rarely. This suggests that routine measurement of plasma lactate should be limited to patients with previous acidemia who reinitiate NRTI therapy and to pregnant women. For symptomatic lactic acidemia (generally >5 mmol/L), NRTIs and other antiretroviral therapy should be ceased. Currently, asymptomatic lactic acidemia should not be treated and should not lead to a change in antiretroviral therapy.
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PMID:Lactic acidemia in infection with human immunodeficiency virus. 1265 78

Nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxic effects resulting in multiple organ disorders. Liver involvement has been associated mainly with severe lactic acidosis and massive steatosis. However, patients with HIV infection who are receiving antiretroviral treatment frequently have mildly abnormal liver test results that, to date, have not been linked unambiguously to the toxic effects of NRTIs. Thirteen patients with HIV infection treated with NRTI-based regimens had low-grade abnormal liver test results associated with digestive and nonspecific general symptoms. Histologic examination of liver samples showed diffuse steatosis in only 6 cases and mild steatosis in the remaining cases, associated with megamitochondria, mild lobular inflammation and necrosis, Mallory bodies, and perisinusoidal fibrosis. In all cases, ultrastructural study disclosed mitochondrial abnormalities. Our work demonstrates that NRTI-induced toxic effects in the liver may occur as indolent nonspecific disease with variable histologic features and emphasizes the diagnostic value of electron microscopy, particularly when diffuse steatosis is absent.
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PMID:Toxic effects of nucleoside reverse transcriptase inhibitors on the liver. Value of electron microscopy analysis for the diagnosis of mitochondrial cytopathy. 1271 Jan 27

In the pre-HAART era, sustained response to single therapy with interferon in patients infected with HCV and HIV without sever immunodeficiency was low (10-23%). The figures were similar to those in HIV-negative people. Results of combination therapy with pegylated interferon (PEG-IFN) and ribavirin in the group of patients infected with HIV and HCV are similar to those observed in the HIV-negative group. The response is > 50%, and the patients who are most benefited are the carriers of genotype 1. Nevertheless, lactic acidosis is reported as a severe side effect, especially in the group who received HAART with nucleosides inhibitors of reverse transcriptase. Several HAART programs include lamivudin for patients infected with HIV and HCV. Molecular hybridation techniques and chain reaction polymerase assays eliminate the hepatitis B virus DNA in 50% of the cases studied. Serological conversion for AgeHB was observed in 35% and AgsHB was eliminated only in 5%. Average period of serological conversion for AgsHB was 8 months; these patients presented high CD4 cell counts and low HIV load. So far, this is the therapy with better results; however, more combinations of lamivudin with tenofovir and adefovir are being studied for patients with resistant viral mutations.
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PMID:[Treatment of chronic hepatitis C in patients coinfected with HIV-HCV/HBV]. 1271 59

There have been recent increases in the number of female participants in HIV clinical trials and the number of studies addressing the influence of sex on HIV infection. The findings of some studies indicate a potential sex differences in the frequency and severity of adverse reactions to antiretroviral drugs. This article reviews the available data on the incidence and characteristics of potential sex differences in adverse reactions to certain nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Adverse effects for which a sex difference has been reported include lactic acidosis, rash, elevation in liver enzymes, dyslipidemia, and insulin resistance. The reasons for these sex differences in adverse drug events are unclear but may include differences between men and women in body mass index and fat composition, hormonal effects on drug metabolism, or the effects of genomic constitutional differences on the levels of various enzymes. These differences warrant further study.
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PMID:Sex differences in adverse reactions to antiretroviral drugs. 1271 43

HAART has resulted in dramatic declines in morbidity and mortality among patients infected with HIV. Increased experience with HAART has led to the detection of drug related toxicities that may compromise adherence and necessitate discontinuation of treatment and alteration of otherwise effective regimens. This article considers the major long-term complications associated with nucleoside reverse transcriptase inhibitor (NRTI) use--hyperlactatemia and lactic acidosis/hepatic steatosis, other hepatotoxicities, pancreatitis, lipodystrophy, lipoatrophy, neuropathy, and hematologic toxicities. Mechanisms by which NRTIs may produce these effects are discussed, as are differential effects of agents in this class and management options.
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PMID:Long-term complications of nucleoside reverse transcriptase inhibitor therapy. 1274 68

Hyperlactataemia is seen in 8-18.3% of HIV-infected patients taking nucleoside-analogue reverse transcriptase inhibitors (NRTIs). Recent epidemiological studies suggest that most episodes are transient and subclinical. However, symptomatic and occasionally life-threatening cases accompanied by metabolic acidosis and hepatic steatosis (ie, lactic acidosis syndrome) have also been described. Though yet to be fully elucidated, the proposed mechanism is NRTI-induced inhibition of mitochondrial DNA polymerase culminating in derangements in oxidative phosphorylation and lactate homeostasis. Signs and symptoms range from mild hyperlactataemia accompanied by nausea, abdominal discomfort, and weight loss to severe, intractable lactic acidosis complicated by coma and multi-organ failure. Significant progress has recently been made with regard to the natural history of NRTI-related hyperlactataemia. However, other important aspects of the disorder, such as its pathogenesis, predisposing conditions, and management, remain poorly understood. This article reviews the current published work on these issues, identifies areas of controversy, and addresses directions for future research.
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PMID:Hyperlactataemia syndromes associated with HIV therapy. 1452 59

Nucleoside reverse transcriptase inhibitors (NRTIs) are effective antiretroviral therapy for the treatment of HIV-infected patients. NRTIs can induce mitochondrial impairment that leads to a number of adverse events, including symptomatic lactic acidosis. In the present review, we describe the underlying mechanism of NRTI-induced toxicity and the main clinical features of this infrequent, but severe, emerging complication. We also summarise experimental data and clinical observations that support the use of L-carnitine supplementation to reverse NRTI-induced mitochondrial impairment.
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PMID:Bench-to-bedside review: severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors. 1279 72


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