Transcript Update on Lipodystrophy

Metabolic Complications
of HIV
Dr Lou Haenel, Jr
Endocrinology
12/10
Terminology
Lipodystrophy
Lipoatrophy
Lipohypertrophy
HIV
HAART (Highly Active Anti-Retroviral
Therapy)
Facial lipoatrophy
Buffalo Hump
Peripheral Lipoatrophy
Body-Fat Abnormalities
Reported in 40-50% of ambulatory HIVinfected patients
Preliminary case definition by DEXA and
CT imaging not ready for widespread
clinical practice
Central fat accumulation tends to be
visceral in location
Location
Visceral (Hepatic, Omental)
Buffalo hump
Breasts
Facial
Neck
Extremities
Etiology
HIV – Direct virus mediated effect
Protease Inhibitor
Nucleoside analogue reversetranscriptase inhibitors
Nonnucleoside reverse transcriptase
inhibitors
Cytokine mediated effect (Adipocytokine)
Pathogenesis
Inhibiting sterol regulatory enhancerbinding protein 1 (SREBP1) mediated
activation of retinoid X and PPARλ
Disruption of adipogenesis
Inhibit mitochondrial DNA polymerase
alpha (DNA replication)
TNFα receptor alteration
Clinical Implications
Physical changes
Hypertriglyceridemia
Low HDL cholesterol
Modest increases in LDL cholesterol
Increased diastolic BP
Increased Metabolic syndrome profile
Increased cardiovascular risk
Update on
Lipodystrophy
Dr. Louis C. Haenel, IV
Endocrinology
UMDNJ-SOM Volunteer Faculty
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%
Dyslipidemia
↑ small, dense LDL 2
↑ apolipoprotein B
More atherogenic profile
↑ free fatty acid levels
↓ clearance of VLDL
.
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
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
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
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 agematched controls
PI therapy may promote atherosclerosis
by ↑ CD-36 dependent cholesterol ester
accumulation in macrophages
Risk Factor Modification
Dyslipidemia
Hypertension
Insulin resistance
Sedentary lifestyle
Weight
Family history
Tobacco
Treatment of Lipodystrophy
Change in HAART therapy
Exercise
Metformin
Thiazolidinediones
Leptin
Recombinant Growth Hormone therapy
Recombinant testosterone therapy
Oral testosterone therapy
Treatment of Metabolic Syndrome
Diet
Exercise
Metformin
Thiazolidinediones
Additional diabetes mellitus treatment
strategies
Treatment of Hypertension
Ace inhibitor therapy
Angiotensin receptor blocker therapy
Hydrochlorothiazide
Beta blocker therapy
Treatment of Dyslipidemia
Fibric Acid derivatives (Tricor, Lopid)
Cholesterol absorption inhibitors (Zetia)
Thiazolidinediones
Statin therapy



Pravachol
Crestor
Beware of Lescol, Zocor, Mevacor
Improvement of Appearance
Surgery
Liposuction
Injectable agents

Polylactic acid (promotes collagen formation)