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Background: Human immunodeficiency virus (HIV) infection and antiretroviral therapy have been associated with non-alcoholic fatty liver disease (NAFLD), but few studies have evaluated whether HIV infection is an independent risk factor for the development of hepatic steatosis and advanced liver fibrosis. Objectives: To study the prevalence and severity of hepatic steatosis and advanced fibrosis in people living with HIV and control outpatients. Methods: We conducted a cross-sectional analysis of relevant data from 875 pairs of individuals belonging to an HIV-dedicated outpatient clinic and an adult primary care clinic of an inner-city hospital. Hepatic Steatosis Index (HSI) and FIB-4 index were calculated as non-invasive measures of steatosis and fibrosis, respectively. A multivariate logistic regression analysis was performed to assess predictors of steatosis and advanced fibrosis. Results: The prevalence of hepatic steatosis, determined by HSI ≥36, was higher in HIV-negative subjects (71.5% vs. 65.4%, p=0.006). The prevalence of advanced fibrosis, determined by FIB-4 index ≥3.25, was higher in the HIV-positive group (7% vs. 1.7%, p Conclusions: In this cohort, hepatic steatosis was more prevalent in non-HIV infected patients, while advanced fibrosis had a higher prevalence in people living with HIV. HIV infection was not found to be an independent risk factor for either hepatic steatosis or fibrosis.

Dysphagia is a symptom with diverse etiologies including luminal narrowing of the esophagus and motility disorders. Arterial vessels are known to compress the esophagus and cause luminal narrowing. However, identifying a pulmonary venous compression of the esophagus rarely occurs in a patient with dysphagia. The technology available at the time of the few prior case reports published more than three decades ago limited the analysis of the pulmonary vessels. We report a case that utilized CT-angiography as well as multiplanar reconstructions and three-dimensional imaging to demonstrate that esophageal compression in the patient presenting with dysphagia was caused by a large left common pulmonary vein.

Background Clostridium difficile infection (CDI) is a leading cause of community-onset and healthcare–associated infection, with high recurrence rates, and associated high morbidity and mortality. We report national rates, leading causes, and predictors of hospital readmission for CDI. Methods Retrospective study of data from the 2013 Nationwide Readmissions Database of patients with a primary diagnosis of CDI and re-hospitalization within 30-days. A multivariate regression model was used to identify predictors of readmission. Results Of 38,409 patients admitted with a primary diagnosis of CDI, 21% were readmitted within 30-days, and 27% of those patients were readmitted with a primary diagnosis of CDI. Infections accounted for 47% of all readmissions. Female sex, anemia/coagulation defects, renal failure/electrolyte abnormalities and discharge to home (versus facility) were 12%, 13%, 15%, 36%, respectively, more likely to be readmitted with CDI. Conclusions We found that 1-in-5 patients hospitalized with CDI were readmitted to the hospital within 30-days. Infection comprised nearly half of these readmissions, with CDI being the most common etiology. Predictors of readmission with CDI include female sex, history of renal failure/electrolyte imbalances, anemia/coagulation defects, and being discharged home. CDI is associated with a high readmission risk, with evidence of several predictive risks for readmission.

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers.72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen.Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups.In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD).Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent.347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence.While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases.

Purpose of review Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Recent findings Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Summary Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

Objective To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Design Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Methods Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Results Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Conclusions Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption.Seven morbidly obese subjects (BMI = 44.5 ± 2.8 kg/m(2)) were studied before and 1 year after GBP with a D: -xylose test. After ingestion of 25 g of D: -xylose in 200 mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of D: -xylose) and carbohydrate absorption using standard criteria.One year after GBP, subjects lost 45.0 ± 9.7 kg and had a BMI of 27.1 ± 4.7 kg/m(2). Gastric emptying was more rapid after GBP. The mean time to appearance of D: -xylose in serum decreased from 18.6 ± 6.9 min prior to GBP to 7.9 ± 2.7 min after GBP (p = 0.006). There was no significant difference in absorption before (serum D: -xylose concentrations = 35.6 ± 12.6 mg/dL at 60 min and 33.9 ± 9.1 mg/dL at 180 min) or 1 year after GBP (serum D: -xylose = 31.5 ± 18.1 mg/dL at 60 min and 27.2 ± 11.9 mg/dL at 180 min).These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1 year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis.

Background/Objective Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM) (age 18.0-39.9 yrs) and an older group with potential bone loss (PoBL) (age 40.0-88 yrs). Subjects/Methods Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole body magnetic resonance imaging. BMD was measured using whole body dual-energy x-ray absorptiometry. Results An inverse correlation was observed between pelvic BMAT and pelvic, total, and spine BMD in the younger PBM group (r=-0.419 to -0.461, P

Gastroenterology (GI) training programs must develop the teaching skills of their faculty and provide feedback to their fellows. Many faculty feel uncomfortable offering feedback or identifying specific areas for improvement to the fellows. We developed an Observed Structured Clinical Exam (OSCE) to assess fellows' skills and provided faculty with specific criteria to rate the fellows' performance. We propose that OSCEs can serve as tools for faculty development in delivering effective feedback.Faculty completed a Web-based training module and received written guidelines on giving feedback. Four OSCE stations were completed by each fellow with faculty using standardized checklists to assess the fellows' skills. Afterwards, faculty rated each program component and assessed their comfort level with feedback.Eight faculty members and 10 fellows from 5 GI training programs in NYC participated. 100% of the faculty agreed that feedback is an important learning tool, should include the learner's self-assessment, and that feedback skills could improve with practice. Compared to faculty skills prior to the program, 87.5% of the faculty agreed that they focused more on specific behaviors and 75% agreed that giving negative feedback was now easier.OSCEs can serve as practicums for faculty development in giving constructive feedback.

Staphylococcus aureus may cause antibiotic-associated diarrhea and enterocolitis, with or without preceding antibiotic use, in immunocompromised adults or infants, or individuals with predisposing conditions, but there is little appreciation of this condition clinically. CLINICAL DISEASE: The main clinical feature that helps to differentiate staphylococcal enterocolitis (SEC) from Clostridium difficile-associated diarrhea is large-volume, cholera-like diarrhea in the former case. A predominance of gram-positive cocci in clusters on gram stain of stool or biopsy specimens and the isolation of S. aureus as the dominant or sole flora support the diagnosis.The pathogenesis of SEC requires the interaction of staphylococcal enterotoxins, which function as superantigens, with interstitial epithelial lymphocytes and intestinal epithelial cells (IECs).Most SEC represents recent S. aureus acquisition, so that improved infection prevention practices can reduce disease recurrence. Management should include aggressive fluid management and repletion and oral vancomycin.

Malnutrition is a frequent problem in persons infected with the human immunodeficiency virus. The origin of malnutrition in patients with AIDS may be multifactorial. The primary mechanisms include disorders of food intake, alterations in intermediary metabolism, and nutrient malabsorption. Attention to the problems of malnutrition in patients with AIDS is of paramount importance because the timing of death in these patients may be more closely related to degree of body cell mass depletion than to any specific underlying infection. Nutritional support can improve nutritional status in selected patients, and repletion of body cell mass may be associated with functional improvement. Early assessment, attention to nutritional requirements, and prompt intervention can minimize wasting and replete body cell mass. This article examines the evidence for malnutrition in patients with AIDS, reviews the studies of nutritional support, and presents an approach to the management of malnutrition in AIDS.

Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

Metabolic complications associated with HIV infection and treatment frequently present as a relative lack of peripheral adipose tissue associated with dyslipidemia and insulin resistance. In this review we explain the connection between abnormalities of intermediary metabolism, observed either in vitro or in vivo, and this group of metabolic effects. We review molecular mechanisms by which the HIV protease inhibitor (PI) class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage. We then propose that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. The excess circulating and dietary lipid metabolites, normally “absorbed” by adipose tissue, are deposited ectopically in lean (muscle and liver) tissue, where they impair insulin action. This process leads to a pathologic cycle of lipotoxicity and lipoatrophy and a clinical phenotype of body fat distribution with elevated waist-to-hip ratio similar to the metabolic syndrome.

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

HIV-infected patients receiving antiretroviral therapy often develop changes in body fat distribution; the dominant change is reduction in sc adipose tissue (SAT). Because adipose tissue makes important hormones involved in whole-body energy metabolism, including leptin and adiponectin, we examined plasma concentrations and their relationship to regional adiposity measured by magnetic resonance imaging in 1143 HIV-infected persons (803 men and 340 women) and 286 controls (151 men and 135 women) in a cross-sectional analysis of the FRAM study.Total and regional adiposity correlated positively with leptin levels in HIV-infected subjects and controls (P0.0001). In controls, total and regional adiposity correlated negatively with adiponectin. In HIV-infected subjects, adiponectin was not significantly correlated with total adiposity, but the normal negative correlation with visceral adipose tissue and upper trunk SAT was maintained. However, leg SAT was positively associated with adiponectin in HIV-infected subjects. Within the lower decile of leg SAT for controls, HIV-infected subjects had paradoxically lower adiponectin concentrations compared with controls (men: HIV 4.1 microg/ml vs. control 7.5 microg/ml, P = 0.009; women: HIV 7.8 microg/ml vs. control 11.6 microg/ml, P = 0.037). Even after controlling for leg SAT, exposure to stavudine was associated with lower adiponectin, predominantly in those with lipoatrophy.The normal relationships between adiponectin levels and total and leg adiposity are lost in HIV-infected subjects, possibly due to changes in adipocyte function associated with HIV lipodystrophy, whereas the inverse association of adiponectin and visceral adipose tissue is maintained. In contrast, the relationship between adiposity and leptin levels appears similar to controls and unaffected by HIV lipodystrophy.

A young male with quiescent hepatitis B presented with sub-acute onset of lower limb weakness found to have an incidental hepatoma that had metastasized to the vertebrae causing an oncologic emergency in the form of spinal cord compression, a rare initial presentation in HBV-related hepatocellular carcinoma (HCC).

Background Hepatoportal sclerosis (HPS) is a cause of noncirrhotic portal hypertension, with patients typically presenting with variceal bleeding. It is idiopathic in nature but is felt to be due to an abnormality of the intrahepatic vasculature. HPS is characterized by varying degrees of portal fibrosis, sclerosis of portal vein branches and dilatation of sinusoidal spaces. Nodular regenerative hyperplasia (NRH), another cause of noncirrhotic portal hypertension, has also been recently described in HIV patients initially diagnosed as having cryptogenic liver disease. Methods/results We describe four cases of HIV+ patients presenting with noncirrhotic portal hypertension; liver biopsies were reviewed by an experienced liver pathologist and found to be consistent with HPS. No other etiologies for their liver disease were found. Conclusions HPS has been recently identified as a cause of noncirrhotic portal hypertension in patients with HIV. It should be considered in the differential diagnosis of HIV patients presenting with variceal bleeding. We postulate that it may be due to intrahepatic microthrombosis or an altered hepatic fibrogenesis related to highly active antiretroviral therapy or due to HIV itself.

Background: Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART). Objective: The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women. Design: Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (S 1 ) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n = 17) and in obese healthy controls (n = 32). Results: The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P < 0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with S, (P < 0.001 for the regression's slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with S, did not differ significantly between groups. For both groups combined, the best model predicting a low S, included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r2 = 0.44, P = 0.0003). Conclusion: In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance.

To compare racial/ethnic differences and effects of HIV on body composition among antiretroviral (ART)-naïve HIV seropositive (HIV+) men to a representative sample of HIV seronegative (HIV-) men. We hypothesized that the effect of HIV infection will be uniform across all racial/ethnic groups.A cross-sectional analysis was performed comparing HIV- (NHANES 1999-2002) and ART-naïve HIV+ men (CPCRA 061). Regional subcutaneous fat area was estimated by skinfold caliper. Total body fat (TBF), fat-free mass (FFM), and body fat index (BFI) were derived by Durnin-Womersley formula (TBF-DW, FFM-DW, BFI [TBF-DW/height(2)]). Bioelectric impedance analyses (BIA) was used to assess TBF-BIA, FFM-BIA, and body cell mass (BCM). Multivariate regression modeling adjusted for age, smoking, and hepatitis C for each measurement was performed.HIV+ men (n = 321) were older and more likely to be smokers than HIV- men (n = 1,996). The HIV- men were heavier in weight (+17.8 kg, p.001) and had higher BMI (+4.3 kg/m(2), p.001), BCM (+2.4 kg, p = .02), FFM (+5.9 kg, p.001), TBF-DW (+5.95 kg, p.001), BFI (+1.6 kg/m(2), p.001), and regional fat mass than the HIV+ men. In the multivariate model, there were significant percentage differences between HIV- and HIV+ African American men for all body composition measurements (weight +15.3%; BMI +14.5%; BCM +5.2%; TBF-DW +15%; BFI 13.9%; FFM-DW 7.9%) and all circumference and skinfold measurements; all ps.05. For Caucasian men, the following differences were significant between HIV- and HIV+: weight +14.4%; BMI +14.0%; BCM +6.0%; TBF-DW +17.7%; BFI 17.1%; FFM-DW 8.7%; and all circumference and skinfold measurements. Similarly, among Latino men the following differences were significant: weight +10.1%; BMI +12.3%; FFM-DW +7.7%; and arm, waist, and thigh circumferences and mid-arm skinfold fat area. The interaction terms for race/ethnicity were not significant across the three racial groups for weight, BMI, BCM, TBF-BIA, and BFI.Compared to HIV uninfected men, among HIV-infected ART-naïve men there was a significant effect of HIV infection itself on body composition among all racial/ethnic groups.

An increased prevalence of insulin resistance, glucose intolerance and diabetes has been reported in HIV infection in the highly active antiretroviral therapy (HAART) era. This development might be clinically significant because of its association with cardiovascular morbidity and mortality as well as the therapeutic challenges of managing polypharmacy. The development of insulin resistance, glucose intolerance and diabetes could be related to the underlying HIV infection, the contribution of different antiretroviral agents, treatment-associated weight gain, immune restoration, as well as the non-HIV related factors. Dissecting these factors in clinical practice might be difficult. Clinical studies include short-term treatments in healthy, non-HIV-infected individuals; randomized, controlled trials; comparative studies of different HAART regimens; and randomized studies of switching regimens in patients with viral suppression and stable immune function. This article reviews the latest knowledge regarding the epidemiology, pathogenesis, prevention and treatment of insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected individuals.

The results of these studies suggested that the growth hormone might play a role in the management of visceral fat accumulation associated with HIV. Analysis of the treatment effect sizes in the published studies show that the effects of various doses of rhGH on trunk fat fit a dose-response characteristic.

To evaluate the efficacy and safety of oxandrolone in promoting body weight and body cell mass (BCM) gain in HIV-associated weight loss.Randomized, double-blind, placebo-controlled trial. Two hundred sixty-two HIV-infected men with documented 10% to 20% weight loss or body mass indexor =20 kg/m were randomized to placebo or to 20, 40, or 80 mg of oxandrolone daily. After 12 weeks, subjects were allowed to receive open-label oxandrolone at a dose of 20 mg for another 12 weeks.Body weight increased in all groups, including the group receiving placebo, during the double-blind phase (1.1 +/- 2.7, 1.8 +/- 3.9, 2.8 +/- 3.3, and 2.3 +/- 2.9 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively; all P0.014 vs. baseline). BCM increased from baseline in all groups (0.45 +/- 1.7, 0.91 +/- 2.2, 1.5 +/- 2.5, and 1.8 +/- 1.8 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively). At 12 weeks, only the gain in weight at the 40-mg dose of oxandrolone and the gain in BCM at the 40- and 80-mg doses of oxandrolone were greater than those in the placebo group, however. Oxandrolone treatment was associated with significant suppression of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and total and free testosterone levels. Treatment was generally well tolerated but accompanied by significant increases in transaminases and low-density lipoprotein as well as decreases in high-density lipoprotein.Oxandrolone administration is effective in promoting dose-dependent gains in body weight and BCM in HIV-infected men with weight loss.

Malnutrition is common in HIV infection. Early studies demonstrated a disproportionate depletion of body cell mass compared to body weight, plus relative expansion of extracellular water volume. Neutron activation studies showed that both potassium and nitrogen were depleted in the HIV+ subjects, whereas cross-sectional imaging documented depletion of skeletal muscle mass. The etiology of malnutrition affects the composition of lost weight. Malnutrition is associated with adverse outcomes, whereas clinical stability is associated with nutritional stability. Increasingly, body composition studies are being incorporated into clinical trials. Hypercaloric feeding promotes gains in weight and body fat, but not in lean mass. Adjunctive therapies include anabolic agents, both steroids and recombinant human growth hormone (rhGH), cytokine inhibitors, and resistance training exercise. In addition to increasing fat-free mass, these therapies also have benefits in quality of life, notably functional performance, as well as physical function. Current research on alterations in body composition in HIV have noted a redistribution of fat, with visceral obesity in patients receiving highly active antiretroviral therapies.

Objective: To investigate the effects of TH9507, a novel growth hormone releasing factor, on abdominal fat accumulation, metabolic and safety parameters in HIV-infected patients with central fat accumulation. Design and methods: Randomized, double-blind, placebo-controlled trial enrolling 61 HIV-infected patients with increased waist circumference and waist-to-hip ratio. Participants were randomized to placebo or 1 or 2 mg TH9507 subcutaneously, once daily for 12 weeks. The primary outcome was change in abdominal fat, assessed by dual energy X-ray absorptiometry and cross-sectional computerized tomography scan. Secondary endpoints included change in insulin-like growth factor-I (IGF-I), metabolic, quality of life, and safety parameters. Results: TH9507 resulted in dose-related physiological increases in IGF-I (P < 0.01 for 1 mg (+48%) and 2 mg (+65%) versus placebo). Trunk fat decreased in the 2 mg group versus placebo (0.8, -4.6 and -9.2%; placebo, 1 and 2 mg, respectively, P = 0.014 for 2 mg versus placebo), without significant change in limb fat. Visceral fat (VAT) decreased most in the 2 mg group (-5.4, -3.6 and -15.7%; placebo, 1 and 2 mg, respectively) but this change was not significant versus placebo. Subcutaneous fat (SAT) was preserved and did not change between or within groups. Lean body mass and the ratio of VAT to SAT improved significantly in both treatment groups versus placebo. Triglyceride and the cholesterol to high-density lipoprotein ratio decreased significantly in the 2 mg group versus placebo. Treatment was generally well tolerated without changes in glucose. Conclusions: TH9507 reduced truncal fat, improved the lipid profile and did not increase glucose levels in HIV-infected patients with central fat accumulation. TH9507 may be a beneficial treatment strategy in this population, but longer-term studies with more patients are needed to determine effects on VAT, treatment durability, and safety.

We report a case of a 39-year-old West African man with unknown human immunodeficiency virus status diagnosed with gastric toxoplasmosis as the presenting manifestation of acquired immunodeficiency syndrome. Toxoplasma gondii is common in severely immunosuppressed patients and most frequently involves the central nervous system, followed by the eye, myocardium and skeletal muscle, lungs, bone marrow, and peripheral blood. For unclear reasons, gastrointestinal involvement is exceedingly rare and occurs in the context of severe immunosuppression and disseminated disease. To our knowledge, this is the first report in the English literature of a patient with isolated, manifest gastric toxoplasmosis without evidence of concomitant cerebral or extracerebral involvement. It is important for both the clinician and the pathologist to maintain a high index of suspicion for toxoplasmosis in immunosuppressed patients presenting with nonspecific symptoms of gastritis and radiologic and endoscopic presence of thickened gastric folds with or without ulceration.

Loss of lean body mass in patients with HIV, commonly referred to as wasting, remains a significant threat to outcome in the era of highly active antiretroviral therapy. It does not require advanced immune deficiency to progress. It is appropriate to reevaluate guidelines for diagnosis and treatment of wasting in the context of the increasing detail with which the risks and causes of HIV wasting are being understood. A wide range of therapies can be effective in preventing weight loss, but the pharmacologic options for restoring body cell mass, a key measure of HIV wasting, are far more limited. A collaborative meeting of clinicians and researchers with an interest in HIV wasting was held to evaluate published guidelines in the context of current clinical data.

The aim of this article is to review the basic biology of infection with HIV-1 and the development of the acquired immunodeficiency syndrome. The discussion will include epidemiology, general description of the retroviruses, pathogenesis of the immune deficiency, clinical consequences, treatment, and treatment outcomes. Aspects of the infection that affect protein and energy balance will be identified.

HIV-associated wasting is defined as > or = 10% involuntary weight loss and includes declines in both lean and fat mass. This large (757 subjects), randomized, double-blind, placebo-controlled trial investigated the efficacy, safety, and tolerability of recombinant human growth hormone (rhGH) in 2 doses-0.1 mg/kg up to a maximum of 6 mg daily (DD) or alternate days (AD)-in the treatment of wasting and weight loss in highly active antiretroviral therapy (HAART)-treated HIV-infected subjects. The evaluable population for ergometry comprised 555 subjects, 87.6% of whom were receiving HAART. At 12 weeks, median maximum work output increased by 2.4 and 2.6 kJ in the AD and DD groups, respectively. The median treatment difference was 2.9 kJ for DD vs. placebo (P < 0.0001). Body weight increased by 2.2 and 2.9 kg in the AD and DD groups, respectively. Corresponding median treatment differences vs. placebo were 1.5 and 2.2 kg (P < 0.0001). Lean body mass (LBM), by bioelectric impedance spectroscopy, increased by 3.3 and 5.2 kg, respectively (P < 0.0001 vs. placebo; P = 0.0173 DD vs. AD), and fat mass, predominately truncal, decreased. Quality of life (QoL) improved significantly in both rhGH groups. Fluid-retention adverse effects and hyperglycemia were more common in the DD than in the AD group. No significant changes in HIV viral load or CD4 cell count occurred. In conclusion, over the 12-week course of therapy, rhGH, 0.1 mg/kg DD, was superior to placebo in improving physical function, body weight, body composition, and QoL and was superior to AD dosing in restoring LBM.

Background: Some HIV-infected patients develop fat maldistribution with visceral adipose tissue (VAT) accumulation and metabolic abnormalities. No medical treatment is approved by the US Food and Drug Administration to reduce VAT. Methods: In this double-blind trial, 245 HIV-infected patients with excess VAT were randomized to receive placebo (PL), recombinant human growth hormone (r-hGH) at a dose of4 mg daily (DD) or4 mg on alternate days (AD) for 12 weeks. For weeks 12 to 24, DD patients were rerandomized to PL (DD-PL) or AD (DD-AD), AD patients continued on AD (AD-AD), and PL patients were switched to DD (PL-DD). Results: From baseline to week 12, VAT decreased significantly compared with PL in DD (-8.6%, P < 0.001) but not in AD (-4.2%, P = 0.052). Trunk-to-limb fat ratio decreased significantly in both (P < 0.001) compared with PL, as did total cholesterol and non-high-density lipoprotein (HDL) cholesterol (-4.5% and -7.5% in DD, -4.3% and -6.2% in AD). At week 24, all groups displayed significant (P < 0.05) reductions in VAT (-5.3% to -9.5%) and trunk fat (-7.8% to -22.8%). DD-AD and AD-AD also displayed significant (P < 0.05) reductions in non-HDL cholesterol. Conclusions: These results suggest that r-hGH dosed at 4 mg daily for 12 weeks decreases VAT and cholesterol concentrations in HIV-infected patients with excess VAT. The optimal regimen to sustain these effects awaits determination.

Objective: The visceral compartment is a surrogate for visceral adipose tissue. Cross-sectional visceral compartment area (VCA) has been approximated from waist circumference using a circular model. However, the two-dimensional shape of the abdomen is rarely circular. This study validated an elliptical model of cross-sectional total abdominal area (TAA), subcutaneous adipose tissue (SAT) area, and VCA at the L4–L5 level. Research Methods and Procedures: We analyzed magnetic resonance images (MRIs) at the level of the L4–L5 intervertebral space from 35 subjects with a wide range of abdominal adiposity. Waist circumference, abdominal thickness (midline sagittal diameter), abdominal width (coronal diameter at one-half of abdominal thickness), and abdominal SAT thickness at four sites (front, back, right, and left) were measured from MRI images using an image analysis software. The same anatomical regions were also estimated from anthropometrics purely by geometric formulae of circular and elliptical models. A simple linear regression model was used to interpret the association strength between anthropometric estimates and MRI measures. Results: Estimated TAA by either model was strongly related to MRI TAA (r2 = 0.98, p < 0.0001). The SAT and VCA by MRI analysis showed a stronger association with calculation from an elliptical model (r2 = 0.95 and 0.88, respectively; p < 0.001) than a circular model (r2 = 0.69 and 0.25, respectively; p < 0.001). The absolute prediction residuals and variances were significantly smaller with an elliptical model than a circular model (p < 0.0001). Discussion: An elliptical anthropometric model might be superior to a circular model to estimate abdominal SAT and VCA.