Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Up-to-date therapy has in recent years substantially modified the clinical course of HIV infections and AIDS. The progress of the disorder has changed-today it is a chronic disease of many years. Already in 1997 and 1998 it transpired that long-term HAART, highly active antiretroviral therapy, produced adverse metabolic changes, which significantly affect the subsequent progress of the disease. The mechanism responsible for these metabolic changes has not, as yet, been fully clarified-in all probability its etiology is multifactorial. Even prior to the introduction of HAART, some metabolic changes were observed in HIV-infected subjects. These changes are, however, not specific for the pathogen concerned, they are generally seen in acute inflammatory reactions. Since the introduction of HAART in 1996 the range of metabolic changes has expanded. Gradually we detect more and more anthropometric, metabolic and coagulation changes, closely resembling changes seen in the metabolic syndrome (SIR, syndrome of insulin resistance), well known from cardiology and internal medicine-dyslipoproteinaemia, insulin resistance, abdominal obesity. A combination of these disorders is clinically significant due to their role in the development of atherosclerosis and their by no means negligible involvement in the onset of ischaemic heart disease. In view of the much lower mean age of HIV-positive subjects the earlier mentioned complications should be expected in much lower age categories than with HIV-negative individuals. The paper discusses the possible pathogenesis and potential mechanisms of metabolic complications related to HAART, its impact on the cardiovascular risk and the possibilities of hypolipidaemic therapy in HIV-positive patients.
 ...
PMID:[Metabolic syndrome and HIV/AIDS disorder]. 1705 72

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARgamma receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA < or = 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 microU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.
 ...
PMID:Insulin resistance and hepatitis C. 1713 67

Injection drug use remains the predominant mode of transmission of hepatitis C virus (HCV) infection. Growing numbers of persons who have been chronically infected with HCV for 20 or more years are coming to medical attention and are at risk for serious complications of chronic infection, including cirrhosis and hepatocellular carcinoma. Factors linked with the development of advanced fibrosis and cirrhosis include age at infection, duration of infection, heavy alcohol use, coinfections with HIV or hepatitis B virus, and male sex. Emerging risk factors for disease progression include steatosis, insulin resistance (and factors associated with the metabolic syndrome), and host genetics.
 ...
PMID:The changing epidemiology and natural history of hepatitis C virus infection. 1716 13

The use of highly active antiretroviral therapy (HAART) has considerably improved the quality of life and has increased the survival of HIV-infected individuals. Although HAART can successfully suppress viral replication in the long term, it is not without significant toxicity, which can seriously compromise treatment effectiveness. Moreover, the rapid rate of virus mutation and subsequent emergence of drug-resistant HIV variants threaten the longer-term efficacy of HIV treatment. The most common adverse effects caused by HAART include a metabolic syndrome with lipodystrophy, hyperlipidemia and insulin resistance, deterioration in the clinical status due to various exaggerated local and systemic inflammatory reactions during the immunerestoration disease, and various hepatic, peripheral and cardiac muscle, kidney, bone, bone marrow, retinal, ear, and skin toxicities. The heterogeneity in the organs affected by the different drugs and the morphological features observed in tissues in HAART-treated patients raise possible explanations including differential distribution or activation of these agents. Antiretroviral drugs from new classes, as well as new drugs from existing classes with favorable resistance and side effect profiles are in various stages of development. However, new tissue disorders will be certainly described in the future in patients treated with these drugs. The different pathophysiology of the main adverse effects and the less common known side effects of antiretroviral therapy against HIV are described here, with special emphasis on the histological features induced by HAART.
 ...
PMID:The pathology induced by highly active antiretroviral therapy against human immunodeficiency virus: an update. 1716 1

Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients.
 ...
PMID:Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications. 1718 14

Highly active antiretroviral therapy incorporating protease inhibitors (PIs) is successful in controlling HIV infection and has dramatically improved the prognosis of HIV-infected patients. The therapeutic benefit of long-term use of HIV PIs is compromised by an increased risk of cardiovascular disease, however, including metabolic syndrome and endothelial dysfunction. Although clinical evidence strongly suggests an association of the use of HIV PIs with endothelial dysfunction, the underlying molecular mechanisms have not been fully elucidated yet. In this review, we describe recent advances in the molecular mechanisms of PI-induced endothelial dysfunction. The available evidence demonstrates that certain HIV PIs could induce endothelial dysfunction, including a decrease of endothelium-dependent vasorelaxation, inhibition of the nitric oxide synthase system, increase of oxidative stress, and activation of mitogen-activated protein kinases. HIV infection itself may also induce endothelial dysfunction and injury. These new discoveries provide a better understanding of the molecular mechanisms of the interaction between HIV PIs and vascular cells and may suggest potential approaches to control HIV PI-associated cardiovascular complications.
 ...
PMID:Molecular mechanisms of HIV protease inhibitor-induced endothelial dysfunction. 1724 28

Bilateral non inflammatory salivary gland enlargement (sialadenosis) is seen with a diverse number of diseases. It is commonly recognized in alcoholism, anorexia and bulimia nervosa and HIV infections. The association between diabetes mellitus and sialadenosis has been reported rarely in the last three decades. We report a patient with sialadenosis in association with metabolic syndrome. We discuss the clinical implications of this novel association including possible regression of salivary gland enlargement with intensive glycemic and lipid control.
 ...
PMID:Marked bilateral parotid enlargement in metabolic syndrome: a case report and review of the literature. 1728 56

We undertook a prospective study to assess the prevalence of the metabolic syndrome (MetS) in HIV patients at the start of highly active antiretroviral therapy (HAART), and at 48 weeks, and we also studied its relationship with high-sensitivity C-reactive protein (hs-CRP) in 60 HIV patients who maintained the same regimen during follow-up. The prevalence of MetS rose from 16.6% at baseline to 25% at 48 weeks (P=0.0001). During follow up, 7/50 patients developed MetS, leading an incidence of 14/100 patients/year. The MetS was associated with age, homosexuality, and lower hepatitis C virus prevalence; only age remained significant in the multivariate analysis (for each five-year increase: beta coefficient 4.26, 95% confidence interval, 3.80-4.75; P=0.0039). The hs CRP values were similar in patients with and without the MetS, and they did not increase at 48 weeks of HAART.
 ...
PMID:Incidence and prevalence of the metabolic syndrome in a cohort of naive HIV-infected patients: prospective analysis at 48 weeks of highly active antiretroviral therapy. 1762 15

The lipodystrophies are characterized by loss of adipose tissue in some anatomical sites, frequently with fat accumulation in nonatrophic depots and ectopic sites such as liver and muscle. Molecularly characterized forms include Dunnigan-type familial partial lipodystrophy (FPLD), partial lipodystrophy with mandibuloacral dysplasia (MAD), Berardinelli-Seip congenital generalized lipodystrophy (CGL), and some cases with Barraquer-Simons acquired partial lipodystrophy (APL). The associated mutant gene products include 1) nuclear lamin A in FPLD type 2 and MAD type A; 2) nuclear lamin B2 in APL; 3) nuclear hormone receptor peroxisome proliferator-activated receptor gamma in FPLD type 3; 4) lipid biosynthetic enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 in CGL type 1; 5) integral endoplasmic reticulum membrane protein seipin in CGL type 2; and 6) metalloproteinase ZMPSTE24 in MAD type B. An unresolved question is whether metabolic disturbances are secondary to adipose repartitioning or result from a direct effect of the mutant gene product. Careful analysis of clinical, biochemical, and imaging phenotypes, using an approach called "phenomics," reveals differences between genetically stratified subtypes that can be used to guide basic experiments and to improve our understanding of common clinical entities, such as metabolic syndrome or the partial lipodystrophy syndrome associated with human immunodeficiency virus infection.
 ...
PMID:Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism. 1737 81

In the HIV infection, the short time-scale between the HIV-induced cardiovascular events and the onset of antiretroviral therapy elicits a thrombophilic co-factor that worsens the induced atherosclerosis. We compared the factor VIII plasma activity, previously implicated in arterial and venous thrombosis, with a surrogate marker of atherosclerosis, the carotid intima-media thickness, and with the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII plasma activity is significantly associated with the carotid intima-media thickness and, strongly, with blood glucose and triglycerides levels. A raised FVIII plasma activity is an important feature of the metabolic syndrome and a putative co-factor of HAART induced cardiovascular events. Thus the prevention of the HAART-induced cardio-vascular events should probably not be exclusively focused on atherosclerosis but likewise on the thrombus formation process.
Curr HIV Res 2007 May
PMID:Correlations between carotid IMT, factor VIII activity level and metabolic disturbances: a cardio-vascular risk factor in the HIV positive persons. 1750 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>