Metabolic Complications of HIV

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

2. Terminology • Lipodystrophy • Lipoatrophy • Lipohypertrophy • HIV • 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 • Breasts • Facial • Neck • Extremities

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 • Dyslipidemia • Hypertension • Insulin resistance • Sedentary lifestyle • Weight • Family history • Tobacco

23. Treatment of Lipodystrophy • Change in HAART therapy • Exercise • Metformin • Thiazolidinediones • Leptin • Recombinant Growth Hormone therapy • Recombinant testosterone therapy • Oral testosterone therapy

24. Treatment of Metabolic Syndrome • Diet • Exercise • Metformin • Thiazolidinediones • 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 • Crestor • Beware of Lescol, Zocor, Mevacor

29. Improvement of Appearance • Surgery • Liposuction • Injectable agents • Polylactic acid (promotes collagen formation)