Didactic Series. Lipohypertrophy in HIV

Transcription

1 Didactic Series Lipohypertrophy in HIV Daniel Lee, MD Clinical Professor of Medicine UCSD Medical Center Owen Clinic August 14th, 2014 ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this educational activity for a maximum of one credit per hour AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. 1

2 Learning Objectives 1) Describe the differences between lipohyertrophy and obesity 2) Review reasons why lipohypertrophy occurs in HIV patients on HAART 3) Describe treatment options for lipohypertrophy 2

3 Definition of Lipodystrophy Lipodystrophy refers to a variety of fat changes that may occur in patients with HIV Primarily 3 main subclasses Fat loss or lipoatrophy (arms, legs, face, buttocks, breast) Not always distinguishable from AIDS-related wasting Fat accumulation or lipohypertrophy (abdomen, back of neck, lipomas, breast) Mixed fat loss and fat gain Lipodystrophy may also be associated with lipid abnormalities (elevated cholesterol and triglycerides) glucose abnormalities (insulin resistance, diabetes) other manifestations

4 Importance of Lipohypertrophy Patient issues Affects body image Neck pain, back pain, respiratory difficulties Affects self esteem May cause or worsen depression Identification of HIV status Doctor/Provider issues Increased cholesterol and triglyceride levels Possible increased risk of heart disease Affects patient adherence to antiretroviral therapy

5 Lipohypertrophy - Question #1 How do you distinguish lipohypertrophy from obesity? List several differences including how you would determine the difference. Please type in the chat box with your answer(s)

6 Lipohypertrophy Answer #1 Lipohypertrophy More associated with visceral adipose tissue (VAT) CT Scan of Abdomen at L4-L5 May include upper trunk fat (including dorsocervical hump, neck fat, fat around latissimus dorsi, gynecomastia, and lipomas) Location upper abdomen Fat texture firmer Fat pinch test minimal SQ fat that is pinchable Obesity More associated with subcutaneous adipose tissue (SAT) May include dorsocervical hump and other fat accumulation, but more evenly distributed Location lower abdomen Fat texture softer Fat pinch test more SQ fat that is pinchable US DHHS and HRSA. Guide for HIV/AIDS Clinical Care. Abnormalities of Body-Fat Distribution Chapter 11, January 2011 Accessed at

7 Lipohypertrophy vs. Obesity

8 Measuring Abdominal Fat by CT (L4-L5) Shaded area below is visceral fat Shaded area below is subcutaneous fat

9 Progression of Lipodystrophy on CT Increasing percentage of visceral fat 40% 70% 90%

10 Lipohypertrophy - Question #2 Name several reasons why lipohypertrophy (fat accumulation) occurs in HIV patients on HAART? Please type in the chat box with your answer(s)

11 Lipohypertrophy Answer #2 Proposed Causes of Fat Gain (Lipohypertrophy) Patient factors Age Race/Ethnicity Gender Higher body mass index (BMI) HAART-related factors Protease inhibitors Return to health phenomenon - expected weight gain with starting any HAART regimen Other Obesity Poor diet Lack of exercise Insulin Resistance Cytokine dysregulation Decreased adiponectin levels Leptin deficiency Growth hormone deficiency Accelerated aging (senescence) Immune Reconstitution Genetics Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. Jun ;353(9170):

12 Lipohypertrophy - Question #3 What is the name of the first and only medication that is FDA-approved to treat HIV-associated lipodystrophy? Please type in the chat box with your answer(s)

13 Lipohypertrophy Answer #3 Tesamorelin Approved in November 2010 for the reduction of excess abdominal fat in HIV patients with lipodystrophy 2 mg SQ daily VAT reduced by 15.4% compared to placebo over 26 wks Improved patient and physician ratings of abdominal profile Statistically significant improvements in TG & TC/HDL ratio Increase in IGF-1 levels and HbA1c Falutz J, Potvin D, Mamputu J, et al. Effects of tesamorelin, a growth hormone releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr 2010;53:

14 Treating Lipohypertrophy Lifestyle changes Diet Exercise Insulin sensitizers Metformin Other drugs Testosterone Anabolic steroids Recombinant human growth hormone Growth hormone releasing factor Surgical interventions Liposuction Surgical removal

15 Summary and Conclusions As HIV+ patients live longer and continue to age (associated with slowing of metabolic rate), clinicians are seeing more patients with fat accumulation Distinguishing lipohypertrophy vs. obesity can sometimes be difficult, but there are specific characteristics that may differ depending on fat type (VAT vs. SAT), location, and texture Pinch test may be helpful to distinguish lipohypertrophy from obesity The exact causes of lipohypertrophy remains unclear, but likely is multifactorial and includes many factors, such as HIV-related factors (HIV, HAART) and non-hiv related factors (aging, genetic predisposition, return to health phenomenon) Effective treatment of lipohypertrophy is limited - tesamorelin

16 Lipohypertrophy References Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. Jun ;353(9170): Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), 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: Grunfeld C, Rimland D, Gibert CL, et al. Association of upper trunk and visceral adipose tissue volume with insulin resistance in control and HIV-infected subjects in the FRAM study. J Acquir Immune Defic Syndr. 2007;46: Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, Assaad H, Turner R, Grinspoon SK. Reduction in Visceral Adiposity is Associated with an Improved Metabolic Profile in HIV-Infected Patients Receiving Tesamorelin. Clin Infect Dis June 1; 54(11): US DHHS and HRSA. Guide for HIV/AIDS Clinical Care. Abnormalities of Body-Fat Distribution Chapter 11, January 2011 Accessed at 601_body-fat_abnormalities.html.