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)

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.
 ...
PMID:Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. 1567

We report a 58-year-old Afro-Caribbean woman who presented with more than 20 dermatofibromas on the body particularly on the back, arms and legs. These developed spontaneously over the course of 5 years. She also had a long-standing 5 x 2-cm area of lipoatrophy on the right upper arm and a 2-year history of several inflammatory subcutaneous nodules developing on the upper chest and left breast. These were confirmed histologically as lupus profundus. Apart from a mild arthritis, she had no other markers for systemic lupus erythematosus and was systemically well. Multiple dermatofibromas are rare. There are around 30 reports of multiple dermatofibromas associated with systemic diseases. More than half of these cases were associated with systemic lupus erythematosus, with or without systemic steroid therapy and about one-third were associated with HIV infection. Although the mechanism is unknown, it appears that multiple dermatofibromas are associated with autoimmune diseases or altered immune states. This is the first case of multiple dermatofibromas associated with lupus profundus. The knowledge of such associations may contribute to the understanding of the pathogenesis of dermatofibromas, which is as yet unknown.
 ...
PMID:Multiple dermatofibromas associated with lupus profundus. 1572 36

HIV-1-infected patients on antiretroviral therapy frequently develop a lipodystrophy syndrome, characterized by peripheral lipoatrophy and visceral fat redistribution associated with metabolic alterations including dyslipidemia and insulin resistance. Its pathophysiology remains unclear but the antiretroviral treatment, associating protease inhibitors (PIs) and nucleoside analogue inhibitors of the viral reverse transcriptase (NRTIs), plays a major role. Some antiretroviral molecules inhibit differentiation and induce insulin resistance and apoptosis in adipose cells both in vitro and in vivo. In vitro, PIs and NRTIs increase the expression and secretion of pro-inflammatory cytokines such as TNF alpha, IL-6 and L-1beta, which are involved in altered adipocyte functions and decrease that of adiponectin, a positive modulator of insulin sensitivity. Similar alterations are observed in fat and serum from HIV-1-infected lipodystrophic patients under antiviral treatment associating PIs and NRTIs. Altered adipokine secretion could result from patients' exposure to PIs and NRTIs and lead to altered adipocyte differentiation, insulin resistance and apoptosis, ultimately resulting in lipoatrophy. These disorders probably result in a decreased secretion of adiponectin and an increased release of free fatty acids by insulin-resistant adipose tissue. Therefore, they could be involved in whole body insulin resistance and metabolic alterations in lipodystrophic HIV-1-infected patients.
 ...
PMID:HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo. 1573 39

The objectives of our study were to describe the characteristics of a subset of patients who had been prescribed serum lactate in clinical practice within a large cohort of HIV-infected patients and to determine the factors associated with hyperlactataemia. Hyperlactataemia (> or =2 mmol/l) was found in 219 [29% (95% confidence interval: 25.3-31.7)] of the 768 HIV-infected participants. In multivariate analysis (logistical regression), an increased risk of hyperlactataemia was associated with increasing age, CD4 count <500/mm3, triglycerides >2.2 mmol/L, lipoatrophy and stavudine use. In a second model coding for the NRTI-based drug combinations, only those including stavudine were associated with an increased risk of hyperlactataemia. In a third model including exposure duration to NRTIs, we estimated a 20% increased risk of hyperlactataemia per year of exposure to didanosine or stavudine. The risk of hyperlactataemia could increase over time in patients treated with these drugs and is also closely associated with increased age, decreased CD4 count, lipodystrophy and increased plasma triglycerides. It could be proposed that patients having one or more of these risk factors undergo regular monitoring of plasma lactate and renal function to prevent lactic acidosis.
 ...
PMID:Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. 1573 22

Resistin is a recently recognized adipocytokine thought to contribute to insulin resistance. We determined resistin levels and metabolic parameters in 24 HIV-infected men and women with lipoatrophy and hyperinsulinemia and studied the effect of 12 wk of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone (4-8 mg/d) on resistin in these subjects. Participants completed metabolic testing before and after rosiglitazone including fasting determination of resistin, adiponectin, and leptin levels, serum inflammatory markers, and hyperinsulinemic euglycemic clamp testing. Resistin concentration decreased significantly after rosiglitazone (12.17 +/- 1.15 ng/ml to 10.23 +/- 1.05 ng/ml; P = 0.02), in conjunction with significant increases in adiponectin- (P < 0.001) and insulin- stimulated glucose disposal (P = 0.004). Leptin levels, as well as TNF-alpha, did not change with rosiglitazone. In summary, among HIV-infected subjects with insulin resistance and lipoatrophy, resistin levels decreased significantly after rosiglitazone. Further investigation into the physiological role of this peroxisome proliferator-activated receptor-gamma-responsive adipocytokine in the metabolic abnormalities associated with HIV is warranted.
 ...
PMID:Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone. 1574 Dec 50

Therapeutic strategies for combating HIV-associated lipodystrophy, and lipoatrophy in particular, have been a major focus of HIV clinical research. The initial impetus focused on protease inhibitor withdrawal strategies, which resulted in improved lipid profiles and insulin resistance but no change in subcutaneous or visceral adipose tissue. Nucleoside reverse transcriptase inhibitor withdrawal strategies, specifically withdrawal of thymidine analogues, have achieved greater success in the reversal of lipoatrophy. In particular, the MITOX extension study demonstrated a 35% improvement in limb fat over a 2 year period after a switch from a thymidine analogue to abacavir. However, recovery from lipoatrophy is a slow process, and limited access to and potential toxicities introduced by alternative therapies can limit switch strategies. The use of thiazolidinediones as agents to reverse lipoatrophy has, unfortunately, been shown to be ineffective, as have alternative therapeutic approaches with agents such as metformin, lipid-lowering agents and growth hormones. Although prevention of lipodystrophy may be the only definitive approach to combat this syndrome, the role of intermittent highly active antiretroviral therapy as a means of reducing the incidence, or slowing the development, of lipodystrophy is currently under evaluation.
 ...
PMID:Therapeutic approaches to combating lipoatrophy: do they work? 1576 Oct 72

Metabolic, opportunistic, and other infectious complications of HIV infection and antiretroviral therapy continue to be major areas of active investigation. This year's Conference on Retroviruses and Opportunistic Infections included many important presentations on the clinical aspects of HIV complications. In each successive year, the studies reported in the area of complications have matured and now include more randomized trials evaluating interventions for the management of HIV complications and more well-designed observational studies with long-term follow-up. This article will review new data presented on metabolic complications, including cardiovascular risk, lipid disorders and lipoatrophy, renal complications, hepatic complications (hepatitis B and C virus infections), tuberculosis, and other bacterial infections.
Top HIV Med
PMID:Complications of HIV disease and antiretroviral therapy. 1584 69

In recent years, lipodystrophy and its related complications have changed from an anecdotal issue into a major problem for HIV-infected patients on antiretroviral therapy. Despite great efforts to achieve a consensus in defining this problem, a simple, readily available definition is still lacking. More comprehensive knowledge of the underlying molecular basis and the natural history of body fat changes and metabolic abnormalities is needed to make progress. Also, an objective assessment of body fat is still to be incorporated in clinical practice, so interventions to prevent or treat body fat changes cannot be adequately monitored. Several objective techniques have been used, and all of them have limitations and advantages. There seems to be a good correlation between different techniques for measuring fat, but that is not the case for detecting fat changes. A huge amount of data have been generated on how to manage lipodystrophy. Nevertheless, there is no clinically proven treatment for any feature of lipodystrophy. The only intervention that has been shown to reverse lipoatrophy is the discontinuation of thymidine analogues, but the results obtained are partial or modest at most. Structured therapy interruptions have become an increasingly popular strategy aimed at preventing or reducing antiretroviral drug toxicity, but little objective data exist on their impact on body composition of HIV-infected patients. The issue of body composition has become extremely important for the adequate management of HIV-infected patients.
 ...
PMID:Current perspectives on HIV-associated lipodystrophy syndrome. 1590 2

Lipodystrophy syndrome comprises several conditions (lipoatrophy; lipohypertrophy; mixed syndrome, often associated with dyslipidemia; and insulin resistance). These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. To elucidate the relative contribution of risk factors of drug, disease, and host to fat redistribution, large epidemiologic studies using multivariate analysis were reviewed. In studies assessing lipoatrophy, the most common statistically significant risk factors were use of specific nucleoside analogues, increasing age, presence of markers of disease severity (CD4/HIV RNA), duration of therapy, and white race. In studies assessing lipohypertrophy, the most common statistically significant risk factors were duration of therapy, markers of disease severity, and protease inhibitor use. The pathogenesis of these disorders is complex, but recent hypotheses and evidence suggest that impairment to adipocyte differentiation, impairment of adipokine regulation, unopposed production of proinflammatory cytokines, dysregulation of 11-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.
 ...
PMID:Redefining lipodystrophy syndrome: risks and impact on clinical decision making. 1601 Jan 59

An informal yet comprehensive literature review of abstracts published in Medline was undertaken to identify papers that reported on how facial aging, lipodystrophy, and facial lipoatrophy affect quality of life. Facial lipoatrophy can erode self-esteem, cause psychological distress, and lead to depression. Persons with HIV infection encounter both stigmatization and marginalization as a result of facial lipoatrophy. In addition to exploring novel antiretroviral therapies that do not result in lipodystrophy, clinicians should consider treatments that correct the appearance of lipoatrophy for patients who feel adversely affected by the condition.
 ...
PMID:Relationship between lipoatrophy and quality of life. 1604 80


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