Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A study on the course of hyperlactataemia during highly active antiretroviral therapy (HAART) and the association between hyperlactataemia and antiretroviral drugs was conducted at the outpatient department, Rigshopitalet, Copenhagen. Lactate levels were monitored in 848 patients during a study period of 1 y. Longitudinal analysis was performed on all human immunodeficiency virus-1-infected patients who had plasma lactate > 2.1 mM. Hyperlactataemia was found in 178 patients (21%), of whom 7 patients needed treatment modification, owing to symptomatic hyperlactataemia in 3 and neuropathy in 4 patients, while 171 remained on unchanged therapy. Lactate levels increased in 20 patients during the study period, but the increases were modest with a mean of 0.6 mM (range 0.1-1.7 mM). The association between antiretroviral drugs and hyperlactataemia was studied using logistic regression in 263 patients with data on their treatment regimen available in electronic form. Only stavudine and ritonavir were significantly associated with hyperlactataemia, with odds ratios of 5.1 and 2.6, respectively. In conclusion, symptomatic hyperlactataemia is uncommon, while asymptomatic hyperlactataemia is a frequent and apparently benign condition unlikely to progress to lactic acidosis. A significant association between stavudine and hyperlactataemia was confirmed. The unexpected association between ritonavir and hyperlactataemia will need confirmation in future studies.
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PMID:Natural history of hyperlactataemia in human immunodeficiency virus-1-infected patients during highly active antiretroviral therapy. 1268 87

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

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.
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PMID:Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study. 1274 80

Lactic acidosis has been reported as a complication associated with antiretroviral therapy; in particular, usually with use of nucleoside reverse-transcriptase inhibitors. We describe a human immunodeficiency virus (HIV)-infected patient with a history of lipodystrophy who presented with hepatic insult associated with documented human granulocytic ehrlichiosis (HGE). Despite a normal serum lactate level before the onset of acute coinfection, the patient developed symptomatic hyperlactatemia while receiving appropriate treatment for HGE. To date, this is the first presentation of symptomatic hyperlactatemia in a patient with HIV infection and HGE.
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PMID:Human immunodeficiency virus infection with human granulocytic ehrlichiosis complicated by symptomatic lactic acidosis. 1280 82

This study reports the case of an obese woman with human immunodeficiency virus type 1 (HIV-1) infection who developed fatal nucleoside-associated lactic acidosis 10 d after she started a weight-loss dietary regimen containing 600 kcal/d. This case suggests that very low-calorie diets may be life threatening for HIV-infected patients receiving nucleoside analogues.
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PMID:Fatal nucleoside-associated lactic acidosis in an obese woman with human immunodeficiency virus type 1 infection on a very low-calorie diet. 1283 66

Nucleoside reverse transcriptase inhibitors (NRTIs), which are used for the treatment of human immunodeficiency virus (HIV) infection have been associated with a wide spectrum of clinical manifestations, including hepatic steatosis, lipodystrophy, myopathy, and lactic acidosis. Such adverse effects are postulated to result from the inhibition of mitochondrial DNA gamma polymerase, which causes the depletion of mitochondrial DNA and eventual the disruption of oxidative phosphorylation. Although cases of severe decompensated lactic acidosis are rare, this syndrome is associated with a high mortality rate. We report upon the first Korean case, of severe lactic acidosis in an acquired immunodeficiency syndrome (AIDS) patient receiving stavudine, an anti-HIV drug.
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PMID:A case of lactic acidosis caused by stavudine in an AIDS patient. 1505 48

An evaluation of the US Food and Drug Administration's Adverse Event Reporting System identified that patients coinfected with human immunodeficiency virus and chronic hepatitis C virus who were treated with a regimen of ribavirin and didanosine, with or without stavudine, were at increased risk for events associated with mitochondrial toxicity, including fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis. In response, the US product labels for didanosine and ribavirin have been revised to caution clinicians against coadministration of these drugs.
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PMID:Nucleoside analogues and mitochondrial toxicity. 1509 36

The availability of highly active antiretroviral therapy (HAART) has resulted in dramatic declines in morbidity and mortality in patients infected with human immunodeficiency virus-1 (HIV-1). However, the success of HAART has been tempered by the recognition of adverse metabolic effects clearly associated with its use. These "metabolic complications" include dyslipidemia, changes in body fat distribution, insulin resistance and glucose intolerance, metabolic bone disease, and lactic acidosis. Guidelines to assist clinicians in the management of these complications have been put forth by various organizations, including the International AIDS Society, the HIV Medicine Association of the Infectious Disease Society of America, and the Adult AIDS Clinical Trials Group.
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PMID:Metabolic complications associated with the use of highly active antiretroviral therapy in HIV-1-infected adults. 1525 41

The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use.
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PMID:Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine. 1528 86


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