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Nanik (Nayri) HatsakorzianTouro University, CAEgriftaIntroductionApproximately 30% of HIV patients suffer from abdominal fat accumulation due to ART.1 In these patients subcutaneous adipose tissue is redistributed and accumulates in access in visceral tissue due to adipocyte differentiation led by pro-inflammatory cytokines triggered by HIV infection. This phenomenon, called lipodystrophy, has been associated with dyslipidemia, increased coronary artery calcification, thus an increase in cardiovascular diseases.1 In addition, it has been shown that lipodytrophy cause significant patient distress and may lead to non-adherence.2 Further studies have shown that low growth hormone (GH) secretion is inversely correlated with excess visceral adipose tissue (VAT) in HIV patients, and increasing endogenous GH may reduce triglycerides (TG) and overall cholesterol levels through inhibition of de novo lipogenesis and increase in fat oxidation. 2Clinical trials of Egrifta (tesamorelin)1,2Two similar randomized placebo-controlled phase III trials (primary phase followed by safety extension phase; 26 weeks each)Inclusion criteria:HIV infected patients (18-65 years old) receiving stable ART for at least 8 weeks CD4 cell counts higher than 100 cells/mm3Viral load < 10,000 copies/mlEvidence of abdominal fat accumulation (waist circumference >= 95 cm (M) 94 (F), and waist to hip ratio >= 0.94 (M) 0,88 (F))Exclusion criteria: Fasting glucose of >= 150 Current or history of type 1 or 2 DMHistory of malignancy or active neoplasmExtension phase subjects were confirmed to have < 150 FBGSubjects for both primary phase and extension phase were evaluated approximately every six weeksPrimary endpoints: Percentage change from baseline of visceral adipose tissue (VAT) (reduction by 8%)Secondary endpoints:IGF-1, triglycerides, total cholesterol to HDL ratio, and patient reported outcome to body imageOverall results from the primary phase:Treatment with tesamorelin was associated with improvement in body image (physician-rated belly profile, belly appearance distress, and for patient reported belly profile No statistically significant treatment-by-gender interaction (effects were similar both in men and women at 26 wk)No significant effects on fasting glucose, fasting insulin or 2 h OGTTMean HbA1c increased 0.14% from baseline in tesamorelin treated groupMean IGF-1 levels increased generally within the physiological range of young adults in tesamorelin-treated patientsOverall results from the extension phase:At week 52 improvements in VAT, trunk fat, waist circumference, triglycerides, total cholesterol, and IGF-1 were sustained in the T-T groupSAT and limb fat were preservedNo changes in glucose or insulin were seen after 52 weeks of tesamorelin in the T-T groupPatients in T-P group regained VAT after switching to placebo (baseline)In T-P group, waist circumference remained reduced from baseline by 2 cm at 52 weeks; however, improvements in belly appearance distress as well as in physician- and patient rated belly profile persisted among T-T group onlyAt week 52, in T-P group, belly appearance and patient-rated belly profile seen at week 26 has lost improvement tendency; however remained different than baselineWeaknesses:Male to female ratio = 85.6/14.4%White to black to Hispanic ratio = 77/13.1/10% Use of lipid lowering agents in tesamorelin arm = 45.7%Strengths:Viral load %: 75 (undetectable), ~17 (50-400), 8 (>400)CD4 cell counts%: 91.2 (>=250), 8.8 (<250)Fasting blood glucose%: ~93 (<=125), 7 (>125)Over 94% compliance ConclusionTesamorelin has been shown to reduce VAT significantly, but the effects are transient and is reversed upon discontinuation of the medicationRe-accumulation to almost baseline levels has been seen upon discontinuationT-T recipients were more likely to have an IGF-1 levels above the upper limit of normal which increases the risks of developing diabetesReduction in cardiovascular risks due to reduction of VAT and TG is only hypothesized and not proven clinically. It remains a judgment call when it comes to potential risks of chronic stimulation of the GH axis vs. potential benefits of reduce CVDReferencesFalutz J. et al, Effects of tesamorelin (TH 9507), a growth hormone releasing factor analog, in Human Immunodeficiency Virus infected patients with excess abdominal fat: A pooled analysis of two multicenter, double-blind placebo controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010. 95(9):4291-4304Bedimo, Roger. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. Dovepress. 2011. (3): 69-79.0-571500Table 2: Changes from baseline in body composition, lipid levels, biochemical measures, glycemic measures, belly image, and HRQOL parameters in the primary efficacy phaseTable 2: Changes from baseline in body composition, lipid levels, biochemical measures, glycemic measures, belly image, and HRQOL parameters in the primary efficacy phase0-571500Table 3: Changes from baseline in body composition, lipid levels, biochemical measures, glycemic measures, belly image, and HRQOL parameters in extension phase0Table 3: Changes from baseline in body composition, lipid levels, biochemical measures, glycemic measures, belly image, and HRQOL parameters in extension phase0-457200Adverse events & SAE in extension phase (26-52 week)Adverse events & SAE in extension phase (26-52 week) ................
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