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)

Liver mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTI) in human immunodeficiency virus (HIV) patients has been associated with a wide range of liver involvement ranging from low-grade hepatotoxicity, asymptomatic lactacidemia to severe liver insufficiency, with massive steatosis and life-threatening lactic acidosis. Considerable efforts have been made in the last few years to establish clinical guidelines to avoid life-threatening NRTI-associated lactic acidosis. However, the important issue of low-grade NRTI-associated hepatotoxicity still needs to be unravelled since its natural history is largely unknown. We have recently reported a series of 13 monoinfected HIV patients with low-grade NRTI-associated toxicity. Our results outlined the heterogeneity of NRTI-induced hepatotoxicity and raised the question of its diagnosis. The present study evaluates the expression of cytochrome oxidase (COX) subunits I and IV, encoded by mitochondrial and nuclear DNA, respectively, in NRTI hepatotoxicity. The aim of our study was to compare the detection rate of mitochondrial abnormalities of immunohistochemistry for COX subunit I with electron microscopy. COX subunit I and IV labeling was performed together with light microscopy and ultrastructural analysis in a series of 55 liver biopsies from HIV monoinfected and HIV-hepatitis C virus coinfected patients. Clinical data were also recorded. Our major findings were: (i) decreased COX subunit I labeling is associated with severe ultrastructural mitochondrial alterations and may represent overt NRTI-induced mitochondrial cytopathy; (ii) mild ultrastructural damage associated with normal COX subunit I labeling is of unknown clinical significance. The results of the study suggest that COX subunit I labeling may be a valuable tool for the diagnosis of mitochondrial liver disease in HIV patients.
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PMID:Alteration of cytochrome oxidase subunit I labeling is associated with severe mitochondriopathy in NRTI-related hepatotoxicity in HIV patients. 1681 Mar 13

Antiretroviral treatments with highly active antiretroviral therapy (HAART) have shown remarkable progress in the past decade and resulted in impressive improvements in life expectancy and quality of life for patients infected with human immunodeficiency virus 1 (HIV-1). Despite the clinical benefits, the management of HIV infection faces many problems. Although HAART is able to suppress the viral load in the plasma, it is unable to eradicate it, and once HAART is initiated, treatment needs to be continued over a lifetime. The side effects of long-term HAART, such as lipodystrophy, lactic acidosis, insulin resistance, and hyperlipidemia, are negative impacts for patients who receive HAART. In addition, patients need to demonstrate high adherence to the therapy to achieve viral suppression and prevent the development of a drug-resistant virus. This review discusses currently recommended antiretroviral treatment strategies, the difficulties with antiretroviral treatments, and current issues regarding HIV management.
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PMID:Current therapy for human immunodeficiency virus infection and acquired immunodeficiency syndrome. 1686 97

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.
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PMID:Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. 1688 61

The introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) infection has led to substantial reduction in morbidity and near-complete suppression of HIV-1 replication. This progress has been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs being particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis, neuropathy, miopathy and lactic acidosis. Beyond the inhibition of DNA polymerase-g using nucleoside analogs, it appears that several physiopathologic mechanisms interact to explain the observed toxicity. At present there is no reliable method to detect subclinical mitochondrial toxicity. There is no proven effective therapy for antiretroviral therapy-associated mitochondrial toxicity other than ceasing the implicated agent, and even with this strategy, resolution of symptoms may be incomplete. Therefore, investigation of mitochondrial toxicity of new compounds or new combinations is of growing interest for the clinical application of antiretroviral agents.
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PMID:[Antiretroviral therapy and mitochondrial toxicity]. 1733 66

Mitochondrial toxicity is a major adverse effect of the nucleoside reverse-transcriptase inhibitors (NRTIs) used for treatment of human immunodeficiency virus type 1 (HIV-1) infection and can result in life-threatening lactic acidosis. The toxicity is due to inhibition of polymerase gamma (Pol gamma), which is required for replication of mitochondrial DNA (mtDNA). Genetic factors could be involved in this process, given that not all NRTI-treated patients experience the toxicity. In 1 patient with lactic acidosis, a novel homozygous Pol gamma mutation (arginine to cysteine at codon 964 [R964C]) was identified at a site close to polymerase motif B, which is highly conserved among family A polymerases. Recombinant R964C Pol gamma showed only 14% activity, compared with that of wild-type Pol gamma. Culture with stavudine significantly reduced mtDNA levels in patient-derived lymphoblastoid cell lines (LCLs) harboring R964C Pol gamma, compared with those in LCLs harboring wild-type Pol gamma. The novel Pol gamma mutation could be associated with the severe lactic acidosis induced by long-term NRTI use.
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PMID:Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. 1743 18

Antiretroviral medications have significantly improved the prognosis of subjects infected by human immunodeficiency virus (HIV). However, long-term complications of these drugs are increasingly recognized as significant causes of morbidity and mortality. Non-alcoholic fatty liver disease (NAFLD), which can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure is one of the more often observed complications in the current clinical practice and the correlation with liver enzyme elevations is controversial. Multiple factors have been considered as possibly correlated to this event in the HIV-infected population, including metabolic abnormalities (such as hyperlipidaemia, hyperglycaemia and being overweight), chronic inflammation, concurrent infection with hepatitis C and B viruses, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTI). HIV-associated syndromes such as lactic acidosis and lypodystrophy are frequently associated with fatty liver disease and a mitochondrial injury has been considered as its possible pathogenetic factor. In particular, treatment containing stavudine and didanosine have proven to be the most commonly implicated in the occurrence of mitochondrial abnormalities. Epidemiologic data to better define the role of predictive factors and drugs associated with the development of NAFLD are still lacking. Furthermore, it remains unclear the better therapeutic management for this condition, even if the current best therapeutic option for NAFLD is the treatment of the underlying disease. Other studies are mandatory to better elucidate the pathogenesis of NAFLD and the optimal therapeutic strategy for the underlying conditions.
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PMID:Steatohepatitis in HIV-infected subjects: pathogenesis, clinical impact and implications in clinical management. 1789 69

The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohipertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.
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PMID:Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus. 1903 Jul 39

Human immunodeficiency virus (HIV) infection is now a chronic manageable disease due to which is it imperative for reviewing various medical emergencies which an individual case may encounter. Emergencies may occur at any stage of the disease. HIV infection is associated with several opportunistic infections/malignancies that may be life threatening and need quick intervention by health care workers. These emergencies could be related to opportunistic infections that are seen at presentation or that occur as the immune system gets weaker, or may be HIV induced diseases like enteropathy and wasting, diarrhea leading to dehydration and its sequel, neurological complication like PML etc. and from complications resulting from use of anti-HIV medication like lactic acidosis, pancreatitis, bone marrow suppression and may include the immune reconstitution syndromes.
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PMID:Emergencies in HIV medicine--part I. 1908 56

In a short span of two and a half decades, HIV/AIDS has emerged as second largest killer disease that has affected mankind. The triple drug antiretroviral therapy (ART) has ensured a reasonably good quality of life to HIV infected individuals. Human immunodeficiency virus (HIV) infection is associated with several opportunistic infections/malignancies that may be life threatening and need quick intervention by health care workers. These emergencies could be related to opportunistic infections that are seen at presentation or that occur as the immune system gets weaker, or may bedue to HIV itself per se. The emergencies could also result from use of antiretroviral drugs like lactic acidosis, pancreatitis, bone marrow suppression and may include the immune reconstitution syndromes. The emergencies due to the opportunistic conditions and HIV per se had been dealt with in detail in the part 1, and this part describes various emergencies that could be encountered due to the administration of the anti retroviral treatment. Some patients may present due to emergencies as a result of co-administration of antiretroviral drugs with drugs used for treatment of some opportunistic infections like ATT etc.
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PMID:Emergencies in HIV--part 2. 1926 5

Oral nucleos(t)ide analogs for the treatment of hepatitis B virus (HBV) infection are well tolerated with minimal side effects. These agents do carry a Food and Drug Administration "black box" warning about the development of fatal lactic acidosis on the basis of data from the human immunodeficiency virus literature. However, no previously published cases of this lethal side effect have been reported in patients undergoing HBV treatment using the current Food and Drug Administration-approved HBV medications. We report a case of HBV reactivation after chemotherapy for leukemia, and the development of fatal lactic acidosis attributed to the use of combination oral HBV medications.
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PMID:Fatal lactic acidosis associated with the use of combination oral medications to treat reactivation of hepatitis B. 1946 28


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