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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many circumstances can induce activation and/or injury of the endothelium that plays a role in the development of vascular complications. Raised plasma levels of endothelial markers such as von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have a prognostic and/or diagnostic value. Human immunodeficiency virus-infected patients (HIV+) have a clustering of conditions that activate or injure the endothelium. Highly active antiretroviral treatment produces adverse effects such as dyslipemia, insulin resistance (IR) and body fat changes (named lipodystrophy syndrome) which may contribute to aggravate their endothelial perturbation. The aim of this study was to measure lipid profile, insulin resistance status, and endothelial markers in 38 HIV+ naive of antiretroviral treatment and 63 HIV+ under highly active antiretroviral treatment (33 with lipodystrophy syndrome and 30 without it). Body fat distribution was also evaluated by dual-energy X-ray absorptiometry (DEXA) analysis. Thirty-one HIV negative subjects were used as controls. We looked for association between variables. Insulin resistance status was a common finding in the four groups. Lipodystrophic patients presented an atherothrombotic lipid profile [elevated levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and apolipoprotein-B (APO-B)] and a strong loss of fat in legs and arms (lipoatrophy). All endothelial markers evaluated in our naive patients were higher as compared to control group. sVCAM-1 in HIV+ under therapy without lipodystrophy syndrome showed significantly decreased levels as compared to naive group (487 vs. 666 ng/ml) and vWF and sTM tended to diminish although they did not show a significant difference (130% vs. 170%, 41 vs. 45 ng/ml, respectively). Lipodystrophic patients showed a tendency to increased levels of endothelial activation markers (sVCAM-1: 500 ng/ml and vWF: 154%) together with significantly increased levels of an endothelial injury marker (sTM: 50 ng/ml) with respect to HIV+ under therapy without lipodystrophy syndrome. Plasma levels of sTM, as an endothelial injury marker, correlated with peripheral lipoatrophy (rho = -0.357) in lipodystrophic patients. In conclusion, despite the beneficial immunology effect of highly active antiretroviral treatment and the apparent decrease in the endothelial perturbation, the patients who develop lipodystrophy present altered endothelial markers and other risk factors, such as IR and dyslipemia, which turn them into a high atherothrombotic risk group.
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PMID:Endothelial markers and HIV infection in the era of highly active antiretroviral treatment. 1289 23

HIV lipodystrophy can be objectively diagnosed using a score derived from the 10 parameters in the HIV lipodystrophy case definition (LDCD). Lipodystrophy severity remains subjectively determined by physical examination and patient assessment. Regional dual-energy x-ray absorptiometry (DEXA) and single-slice abdominal computed tomography (CT) scanning are objective but are gender-dependent body composition measures. The LDCD score may provide a means of generating an objective and lipodystrophy grading/severity scale applicable to both men and women. Total and regional clinical lipodystrophy severity scores (generated using the HIV Outpatient Study [HOPS] scale: nil (0), mild (1), moderate (2), and severe (3) lipoatrophy or fat accumulation in 8 body regions) were correlated with objective measures of LD (LDCD score, DEXA, abdominal CT) and metabolic (lipid, glycemic, acid-base) parameters known to correlate significantly with lipodystrophy severity. Analysis was based on 417 lipodystrophic adults and 371 controls recruited to the HIV LDCD study. Correlation coefficients were used to compare physician and patient assessments (rPhysician, rPatient) with objective LD measures and metabolic parameters. The strongest objective correlate of total clinical lipodystrophy severity was the LDCD score (rPhysician = 0.641 [95% CI, 0.584-0.698]; rPatient = 0.620 [95% CI, 0.561-0.678]), whereas the strongest imaging correlate (trunk:limb fat ratio on DEXA) was significantly lower (rPhysician = 0.483 [95% CI, 0.420-0.546]; rPatient = 0.475 [95% CI, 0.412-0.538]; P < 0.001). The LDCD score also yielded significantly greater correlations with 7 of the 8 metabolic parameters than did clinical lipodystrophy severity scores. Based on quartiles of physician-rated severity, the LDCD scores were categorized to allow for rating of lipodystrophy as absent (LDCD score < 0), grade 1 (0-9.9), grade 2 (10-14.9), grade 3 (15-22.9), and grade 4 (>or=23). In conclusion, the LDCD score is the best objective measure of lipodystrophy severity and, in contrast to DEXA and CT, it is also gender independent. Subjective assessment of lipodystrophy severity could possibly be abandoned in cross-sectional studies. The LDCD score and its derived lipodystrophy grading scale merit prospective evaluation.
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PMID:An objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score. 1290

Ten HIV-infected nucleoside reverse transcriptase inhibitor-treated subjects with lipoatrophy or sustained hyperlactatemia were given antioxidants: vitamins C, E, and N-acetyl cysteine. After 24 weeks, anthropometrics did not change significantly, except for a modest decrease in the waist-to-hip ratio. Fasting low-density lipoprotein cholesterol trended toward lower values. Fasting glucose significantly increased along with a significant increase in homeostatic model assessment values, reflecting an increase in insulin resistance. Controlled trials are required to evaluate directly the effects of these agents on lipid and glucose metabolism.
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PMID:Effect of antioxidants on glucose metabolism and plasma lipids in HIV-infected subjects with lipoatrophy. 1290 5

Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as insulin resistance and lipodystrophy, that is, atrophy of subcutaneous fat and accumulation of intra-abdominal fat. Currently, there is no pharmacological treatment for lipoatrophy. Glitazones, a novel class of insulin-sensitizing anti-diabetic agents, increase subcutaneous fat in patients with type 2 diabetes. There are no controlled studies of glitazones in patients with HAART-associated lipodystrophy (HAL). In this randomized, double-blind, placebo-controlled study, 30 patients with HAL received either rosiglitazone (8 mg daily) or placebo for 24 weeks. Baseline characteristics were compared to a group of 30 age-, sex- and weight-matched HIV-negative controls. At baseline, patients with HAL had 1.8-fold (P<0.001) more intra-abdominal and 2.4-fold (P<0.05) more liver fat than HIV-negative controls, who had 1.8-fold (P<0.001) more subcutaneous fat than the patients. After 24 weeks of treatment, rosiglitazone had no effect on body weight, subcutaneous or intra-abdominal fat (magnetic resonance imaging), total body fat (bioimpedance analysis), anthropometric measurements or serum leptin concentrations (a circulating marker of adipose tissue mass). However, rosiglitazone decreased % liver fat (spectroscopy) and serum insulin concentrations, and normalized liver function tests. During the first 12 weeks of rosiglitazone treatment, serum triglycerides increased from 3.5 +/- 0.5 to 6.5 +/- 2.0 mmol/l (from 310 +/- 44 to 575 +/- 177 mg/dl) (P<0.05) and serum cholesterol from 6.0 +/- 0.4 to 7.8 +/- 0.7 mmol/l (from 232 +/- 15 to 301 +/- 27 mg/dl) (P<0.01). Contrary to data in other patient groups, rosiglitazone did not increase subcutaneous fat in patients with HAL after 24 weeks of treatment. Rosiglitazone seemed to ameliorate insulin resistance judged by the decreased serum insulin concentrations and % liver fat. Rosiglitazone unexpectedly caused significant increases in serum triglyceride and cholesterol concentrations, which must be carefully monitored if glitazones are used in these patients.
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PMID:Rosiglitazone in the treatment of HAART-associated lipodystrophy--a randomized double-blind placebo-controlled study. 1292 36

We studied aspects of metabolism in subcutaneous adipose tissue (SAT) in 40 human immunodeficiency virus (HIV)-infected subjects with and without lipodystrophy and in healthy control subjects. HIV-infected subjects without lipodystrophy had less SAT and visceral adipose tissue (VAT). Glycerol release was higher in both HIV-infected groups, especially those without fat redistribution. Tumor necrosis factor (TNF) release from SAT and serum soluble TNF receptor 2 concentrations were significantly higher in HIV-infected individuals with lipodystrophy. The absolute production of acylation-stimulating protein (ASP) and the percentage conversion of the complement protein to ASP were significantly lower in HIV-infected subjects with lipodystrophy. Further studies are needed to dissect the factors that mediate lipoatrophy in HIV infection.
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PMID:Studies of adipose tissue metabolism in human immunodeficiency virus-associated lipodystrophy. 1294 74

I would like to focus on metabolic alterations, and the problems associated with them such as dyslipidemia, insulin resistance, fat loss or lipoatrophy, and fat accumulation. There are also conditions such as bone disease, hyperlactatemia, and other complications. It is not clear whether these problems are just toxicities of the drugs, how they are related to HIV independent of treatments, and whether they belong in discussions of metabolic complications. For the purposes of this discussion, I would like to consider each problem individually while also recognizing overlapping elements in an effort to understand complex etiologic interrelationships.
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PMID:Metabolic abnormalities in patients with HIV infection. 1296 60

Combination of antiretroviral drugs has dramatically improved the prognosis of individuals with HIV infection. However, their long-term benefit is limited by two main factors: the selection of drug-resistant strains and side effects. A large part of the toxicity of antiretroviral drugs has been associated with mitochondrial damage. Nucleoside analogue reverse transcriptase inhibitors (NRTI), which lack the hydroxyl group needed for further DNA chain elongation, block HIV reverse transcriptase. These nucleosides can be mistaken as natural substrates by the polymerase gamma, the enzyme responsible for the replication of mitochondrial DNA (mtDNA). Depletion or damage of mtDNA may affect the aerobic metabolism of carbohydrates and lipids, resulting in the accumulation of pyruvate/lactate and fatty acids, and ultimately in lactic acidosis and lipoatrophy, respectively. However, the relationship between hyperlactatemia and/or lipoatrophy and mtDNA depletion due to NRTIs has not been demonstrated conclusively. The design of methods to measure mtDNA may help to recognize the mitochondrial toxicity of antiretroviral therapy.
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PMID:[Mitochondrial damage by antiretrovirals: diagnosis and monitoring]. 1449 88

The exact mechanism of lipoatrophy remains unclear. One hypothesized mechanism is accumulation of reactive oxygen free radicals, which is possibly related to dysfunctional mitochondria. We evaluated plasma levels of F2-isoprostanes-the most accurate method to measure oxidant stress in vivo-in a group of 59 nucleoside reverse transcriptase inhibitor-treated HIV-1-infected subjects. All had serial measurements of venous lactate levels as well as clinical evaluations for assessment of lipoatrophy and symptoms of mitochondrial toxicity. Overall, 16 subjects had sustained hyperlactatemia (4 of whom were symptomatic) and 43 had serial normal lactate levels. We found a significant increase in circulating products of lipid peroxidation, F2-isoprostanes (nanograms per milliliter), in subjects with lipoatrophy when compared with subjects without lipoatrophy (0.060 +/- 0.025 vs. 0.0420 +/- 0.02, respectively; P = 0.02). Interestingly, there was no significant difference in F2-isoprostane levels (nanograms per milliliter) between patients with persistently normal lactate and those who exhibited a sustained asymptomatic hyperlactatemia (0.053 +/- 0.027 vs. 0.053 +/- 0.021, respectively; P > 0.05). This could be explained by the yet unclear significance of asymptomatic hyperlactatemia, even in a setting like ours, where lactate levels were measured with close attention to the method of collection and processing. In contrast, the 4 subjects with symptomatic hyperlactatemia/lactic acidosis had a significant increase in their F2-isoprostanes compared with subjects with asymptomatic sustained hyperlactatemia (0.082 +/- 0.021 vs. 0.053 +/- 0.021, respectively; P < 0.05).
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PMID:Lipid oxidative markers are significantly increased in lipoatrophy but not in sustained asymptomatic hyperlactatemia. 1450 92

Adipose tissue alterations (ATAs) were clinically assessed in 2258 HIV-1-infected outpatients consecutively observed in 6 Italian clinical centers and were found to be present in 29.5% of the men and 41.9% of the women. A logistic regression model including age, HIV disease Centers for Disease Control stage, CD4 cell counts, HIV RNA load, the duration of antiretroviral therapy, the number of drugs taken, and the use of d4T showed that men had a 0.47 adjusted risk of presenting with ATAs (95% CI: 0.38-0.58, P < 0.0001). The risks of having ATAs (except circumscribed lipomas) in any body region, presenting with fat accumulation, or being affected by combined forms of ATA were also lower in men, whereas the risk of developing pure lipoatrophy was similar in the 2 genders. Our results indicate that women are at higher risk of developing antiretroviral treatment-related ATAs and show a particular and complex ATA pattern.
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PMID:Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns. 1450 94

Cardiovascular complications in the course of human immunodeficiency virus (HIV) infection are multifactorial and may be caused by the virus itself or by the related opportunistic infections and neoplasms. Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients candidate to antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines.
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PMID:HIV infection, highly active antiretroviral therapy and the cardiovascular system. 1452 10


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