Louis Haenel, IV, DO Endocrinology

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 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

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

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

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

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%

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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 age-matched 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)

Thyroid Infectious and Infiltrative Diseases Laboratory Medication

Infectious/Infiltrative Diseases CMV*MAI Cryptococcus*PCP Kaposi’s Sarcoma True Infection vs Postmortem Findings Inflammatory Thyroiditis

Laboratory Findings Lowered T3 Levels * 46 patients evaluated and found to have  T3 levels and normal TSH in stable HIV * T3 levels on admission correlated to mortality in 3 separate studies * T3 seems to follow typical trend seen in euthyroid sick individuals but rT3 levels remain low in asymptomatic and ill pts.

Thyroid Labs TBG levels are  with normal CBG & SHBG TSH values in stable HIV are higher on average than controls with the absolute levels in the upper limit of normal Normal pulse frequency and  amplitude Role of cytokines -- IL-6 and TNF

HIV Related Medications Rifampin (used in the treatment of MAI prophylaxis) induces hepatic microsomal enzymes and increases thyroid hormone clearance Results >  T4 (T4 replace requires  dose) normal T3  rT3 no change in TSH