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Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

ABSTRACT: Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes.In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with ?8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders.Compared with tesamorelin nonresponders, responders experienced greater mean (±SD) reduction in triglyceride levels (26 weeks: -0.6 ± 1.7 mmol/L vs -0.1 ± 1.2 mmol/L [P = .005]; 52 weeks: -0.8 ± 1.8 mmol/L vs 0.0 ± 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 ± 16 mg/dL vs 5 ± 14 mg/dL [P = .01]; 52 weeks: -1 ± 14 mg/dL vs 8 ± 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 ± 0.3% vs 0.3 ± 0.4% [P < .001]; 52 weeks: 0.0 ± 0.3% vs 0.2 ± 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT.In contrast to nonresponders, HIV-infected patients receiving tesamorelin with ?8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. CLINICALTRIALS.GOV REGISTRATION: NCT00123253, NCT00435136, NCT00608023.

SUBMITTER: Stanley TL

PROVIDER: S-EPMC3348954 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

Stanley Takara L TL Falutz Julian J Marsolais Christian C Morin Josée J Soulban Graziella G Mamputu Jean-Claude JC Assaad Hani H Turner Ralph R Grinspoon Steven K SK

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20120410 11

<h4>Background</h4>Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes.<h4>Methods</h4>In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to re ...[more]

PMID: 22495074

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Project description:ImportanceAmong patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone-releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown.ObjectiveTo investigate the effect of tesamorelin on visceral and liver fat.Design, setting, and patientsDouble-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston. The first patient was enrolled on January 10, 2011; for the final patient, the 6-month study visit was completed on September 6, 2013.InterventionsParticipants were randomized to receive tesamorelin, 2 mg (n=28), or placebo (n=22), subcutaneously daily for 6 months.Main outcomes and measuresPrimary end points were changes in visceral adipose tissue and liver fat. Secondary end points included glucose levels and other metabolic end points.ResultsForty-eight patients received treatment with study drug. Tesamorelin significantly reduced visceral adipose tissue (mean change, -34 cm2 [95% CI, -53 to -15 cm2] with tesamorelin vs 8 cm2 [95% CI, -14 to 30 cm2] with placebo; treatment effect, -42 cm2 [95% CI, -71 to -14 cm2]; P = .005) and liver fat (median change in lipid to water percentage, -2.0% [interquartile range {IQR}, -6.4% to 0.1%] with tesamorelin vs 0.9% [IQR, -0.6% to 3.7%] with placebo; P = .003) over 6 months, for a net treatment effect of -2.9% in lipid to water percentage. Fasting glucose increased in the tesamorelin group at 2 weeks (mean change, 9 mg/dL [95% CI, 5-13 mg/dL] vs 2 mg/dL [95% CI, -3 to 8 mg/dL] in the placebo group; treatment effect, 7 mg/dL [95% CI, 1-14 mg/dL]; P = .03), but changes at 6 months in fasting glucose (mean change, 4 mg/dL [95% CI, -2 to 10 mg/dL] with tesamorelin vs 2 mg/dL [95% CI, -4 to 7 mg/dL] with placebo; treatment effect, 2 mg/dL [95% CI, -6 to 10 mg/dL]; P = .72 overall across time points) and 2-hour glucose (mean change, -1 mg/dL [95% CI, -18 to 15 mg/dL] vs -8 mg/dL [95% CI, -24 to 8 mg/dL], respectively; treatment effect, 7 mg/dL [95% CI, -16 to 29 mg/dL]; P = .53 overall across time points) were not significant.Conclusions and relevanceIn this preliminary study of HIV-infected patients with abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and additionally with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings.Trial registrationclinicaltrials.gov Identifier: NCT01263717.

Project description:BACKGROUND: Long term use of antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLWHIV) is associated with disturbances in blood lipids which should be monitored. More data on such disturbances are needed in Cameroon to persuade the country program to institute their routine monitoring. We then sought to determine the prevalence and timing of dyslipidaemia in PLWHIV and receiving ART in a predominantly rural Cameroonian setting. METHODS: A cross-sectional study conducted between August and October 2012 in HIV-infected persons aged 15 years or more and receiving first-line ART for at least six months at The Nkongsamba Regional Hospital in Cameroon. Lipid assays were carried out by enzymatic-linked colorimetric methods. A multiple logistic regression model was used to assess for factors related to dyslipidaemia. RESULTS: Included were 114 participants of whom 83 (72.8%) were females. Their median age was 43 years (IQR: 36-51) and their median CD4 count was 436 cells/?l (IQR: 275-585) after a median duration on ART of 36 months (IQR: 12-60). The prevalence of dyslipidaemia was 70.2%. Hypercholesterolaemia was observed in 34 (29.8%) patients. One-third of them had a high LDL-cholesterol level (LDL-c?130 mg/dl). Hypertriglyceridaemia (TG?150 mg/dl) was present in 59 (51.8%) cases. The proportion of patients with a low HDL-cholesterol (HDL-c<40 mg/dl) was 18.4% while those with a ratio of TC/HDL-c?5 were about 16.7%. A duration of 2-4 years on ART (adjusted Odd Ratio, aOR=5.22, 95% CI: 1.43-19.06, p=0.01), current smokers (aOR=15.94, 95% CI: 1.13-225.61, p=0.04) and a concurrent metabolic disease (aOR=12.54, 95% CI: 1.02-153.86, p=0.48) were independently associated with pro-atherogenic LDL-c values. Alcohol users had a more friendly LDL-c profile (aOR=0.24, 95% CI: 0.07-0.74, p=0.01). CONCLUSION: The study has demonstrated a high prevalence of dyslipidaemia in HIV-patients receiving first-line ART in a predominantly rural setting of Cameroon. There is a need for the country HIV program to institute laboratory monitoring of blood lipids in patients over two years on first line ART with a focus on smokers.

Project description:BackgroundVisceral adiposity is an important risk factor for cardiometabolic diseases.ObjectiveTo determine whether the Metabolic Score for Visceral Fat (METS-VF) is more effective than other adiposity indices in predicting visceral fat area (VFA).MethodsIn this single-center and cross-sectional study, we included patients aged 20-50 years, without diabetes and coronary artery disease, who underwent computed tomography (CT) including the third lumbar vertebra. Age, blood pressure, waist circumference (WC), hip circumference, fasting lipids, and glucose were assessed. VFA was measured by cross-sectional examination of CT. The correlation of WC, body mass index (BMI), waist-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), and METS-VF with VFA was analyzed by correlation analysis. The cut-off values and area under the curve (AUC) for identifying increased VFA (>130 cm2) were determined.ResultsWe included 185 individuals with mean age 38.2 ± 8 and female predominance (58.4%). There was a significant positive correlation between all indices and VFA (p<0.001). ROC analysis revealed that METS-VF and WC demonstrated the highest predictive value for identifying increased VFA. In both men (p=0.001) and women (p<0.001), METS-VF (AUC 0.922 and 0.939, respectively) showed a significant superiority over ABSI (AUC 0.702 and 0.658, respectively), and VAI (AUC 0.731 and 0.725, respectively). Additionally, in women, its superiority over WHR (AUC 0.807) was also statistically significant (p=0.003). We identified a METS-VF cut-off point >6.4 in males >6.5 in females and WC cut-off point >88 cm in males (AUC 0.922), >90.5 cm in females (AUC 0.938).ConclusionMETS-VF is strongly associated with visceral adiposity and better to predict increased VFA. However, its superiority over WC, BMI, BRI, and LAP was not significant. The results emphasize that WC is more appealing as screening indicator for visceral adiposity considering its easy use.Clinical trial registry nameClinicaltrials.gov (http://www.clinicaltrials.gov).Clinical trial registry urlhttps://clinicaltrials.gov/ct2/show/NCT05648409.Clinical trial registry numberNCT05648409.

Project description:People Living with HIV (PLHIV) are often dealing with a range of issues that make life more difficult because of the limited emotional, spiritual, psychological, social, physical and clinical support which consequently lead to poor physical health and quality of life. The holistic care of individuals infected with HIV/AIDS involves promoting psychological and physiological well-being as well as fostering socio-cultural relationships and supporting the fulfillment of spiritual aspirations. We conducted a retrospective cross-sectional study among HIV-infected patients receiving a holistic approach of care model from January 2015 to December 2018 in Kampala district, Uganda. The study involved adult individuals aged 18 and above from whom demographics and other information were obtained. All eligible participants were selected using stratified random sampling from the parishes and systematic random sampling to select study participants. We investigated the clinical profile and the factors associated with viral load suppression among HIV-infected patients receiving a holistic approach of care model in Kampala District. The data was analyzed using STATA version 13. 0. Results: A total of 910 patients were enrolled. 676 (74.3%) were female; 453 (49.8%) were between 18 and 39 years. 324 (35.6%) were either overweight or obese. 769 (84.5%) had viral load beyond detectable limits, 904 (99.3%) were adhering to HIV treatment. 867(95.3%) were virally suppressed. The age group 40-59 years (Adjusted Odds Ratio (aOR) = 2.85, 95% Confidence Interval (CI):1.36-5.97, P = 0.005) and good adherence (aOR = 12.9, 95%CI:1.86-81.07, P = 0.009) were significantly associated with viral load suppression. Conclusion: The holistic care model supports patients in all facets of their lives, resulting into improved treatment outcomes. Our findings show that age and adherence are linked to viral load suppression among HIV-infected adults receiving a holistic approach of care model.

Project description:ObjectivePatients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown.DesignPopulation-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015.SettingVeterans Health Administration hospitals and clinics throughout the United States.ParticipantsTreatment-naive patients with HIV infection (N = 9500).Antiretroviral exposuresInitiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs).Main outcome/effect size measuresIncidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting.ResultsIncidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively.ConclusionAmong treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.

Dataset Information

Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

Publications

Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

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