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
4
(No Transcript)
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 PPAR?
• Disruption of adipogenesis
• Inhibit mitochondrial DNA polymerase alpha (DNA
  replication)
• TNFa 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 (gt240 mg/dl)
• Triglyceride elevation seen in 40 pts (gt200
  mg/dl)
• HDL lt35 mg/dl seen in 27

14
Dyslipidemia

• ? small, dense LDL 2
• ? apolipoprotein B
• More atherogenic profile
• ? free fatty acid levels
• ? clearance of VLDL

15
.
16
(No Transcript)
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 ppara 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

21
(No Transcript)
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

25
(No Transcript)
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

28
(No Transcript)
29
Improvement of Appearance

• Surgery
• Liposuction
• Injectable agents
• Polylactic acid (promotes collagen formation)