1. Metabolic Complications of HIV Dr Lou Haenel, Jr Endocrinology 12/10

2. Terminology LipodystrophyLipoatrophyLipohypertrophyHIV HAART (Highly Active Anti-Retroviral Therapy)

3. Facial lipoatrophy

5. Buffalo Hump

6. Peripheral Lipoatrophy

7. Body-Fat Abnormalities Reported in 40-50% of ambulatory HIV- infected patients Preliminary case definition by DEXA and CT imaging not ready for widespread clinical practice Central fat accumulation tends to be visceral in location

8. Location Visceral (Hepatic, Omental) Buffalo hump BreastsFacialNeckExtremities

9. Etiology HIV – Direct virus mediated effect Protease Inhibitor Nucleoside analogue reverse- transcriptase inhibitors Nonnucleoside reverse transcriptase inhibitors Cytokine mediated effect (Adipocytokine)

10. Pathogenesis Inhibiting sterol regulatory enhancer- binding protein 1 (SREBP1) mediated activation of retinoid X and PPARλ Disruption of adipogenesis Inhibit mitochondrial DNA polymerase alpha (DNA replication) TNFα receptor alteration

11. Clinical Implications Physical changes Hypertriglyceridemia Low HDL cholesterol Modest increases in LDL cholesterol Increased diastolic BP Increased Metabolic syndrome profile Increased cardiovascular risk

12. Update on Lipodystrophy Dr. Louis C. Haenel, IV Endocrinology UMDNJ-SOM Volunteer Faculty

13. Dyslipidemia Cholesterol elevation seen in 27% pts on combination tx (>240 mg/dl) Triglyceride elevation seen in 40% pts (>200 mg/dl) HDL <35 mg/dl seen in 27%

14. Dyslipidemia ↑ small, dense LDL 2 ↑ apolipoprotein B More atherogenic profile ↑ free fatty acid levels ↓ clearance of VLDL

15. .

17. Carbohydrate Metabolism Impaired glucose tolerance seen in more than 35% of HIV infected pts compared to 5% in age and BMI matched controls DM was 3.1X as likely to develop in HIV pts treated with combination therapy vs control population

18. Pathogenesis ↑ circulating free fatty acids Accumulation of intramyocellular lipids Low level of adiponectin Reduced pparα activity which leads to reducing glucose transport mediated via Glut4 transporter Reduce Beta cell insulin secretion

19. Assessment Before initiating HIV therapy, patients should be tested for fasting blood glucose and cholesterol levels Rechecked several weeks after change in therapy and yearly Oral glucose tolerance test

20. Cardiovascular Disease Diabetes Mellitus is considered a coronary risk equivalent Established risk factors Hypertension is seen at higher rates in patients in HAART therapy than for age- matched controls PI therapy may promote atherosclerosis by ↑ CD-36 dependent cholesterol ester accumulation in macrophages

22. Risk Factor Modification DyslipidemiaHypertension Insulin resistance Sedentary lifestyle Weight Family history Tobacco

23. Treatment of Lipodystrophy Change in HAART therapy ExerciseMetforminThiazolidinedionesLeptin Recombinant Growth Hormone therapy Recombinant testosterone therapy Oral testosterone therapy

24. Treatment of Metabolic Syndrome DietExerciseMetforminThiazolidinediones Additional diabetes mellitus treatment strategies

26. Treatment of Hypertension Ace inhibitor therapy Angiotensin receptor blocker therapy Hydrochlorothiazide Beta blocker therapy

27. Treatment of Dyslipidemia Fibric Acid derivatives (Tricor, Lopid) Cholesterol absorption inhibitors (Zetia) Thiazolidinediones Statin therapy Pravachol Pravachol Crestor Crestor Beware of Lescol, Zocor, Mevacor Beware of Lescol, Zocor, Mevacor

29. Improvement of Appearance SurgeryLiposuction Injectable agents Polylactic acid (promotes collagen formation) Polylactic acid (promotes collagen formation)