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Metabolic Consequences of HIV and its Treatment

I. Lipid Metabolism

A. Abnormalities of lipid metabolism in the pre-HAART era

1. Hypertriglyceridemia

2. Decreased LDL and HDL cholesterol levels

3. Increased free fatty acid levels

4. Decreased LPL activity and TG clearance rates

5. Increased rates of whole body lipolysis and nonoxidative lipid disposal

6. Increased rates of de novo lipogenesis

B. Abnormalities of lipid metabolism with HAART, particularly protease inhibitors

1. Further increases in TG levels, particularly with ritonavir

2. Increased LDL cholesterol levels

3. No significant change in HDL cholesterol levels

II. Glucose Metabolism

A. Abnormalities of glucose metabolism in the pre-HAART era

1. Fasting glucose similar to or slightly lower than HIV-negative controls

2. Increased insulin sensitivity (euglycemic, hyperinsulinemic clamp)

3. Other catabolic states typically characterized by insulin resistance

B. Abnormalities of glucose metabolism with HAART, particularly protease inhibitors

1. Modest increases in fasting glucose levels

2. Proportionately greater increase in insulin levels; increased insulin/glucose ratio, suggesting insulin resistance

3. Frank diabetes mellitus rare

III. Alterations in Body Shape

A. Dorsocervical fat pad enlargement

1. Seen classically with glucocorticoid excess (Cushing's syndrome)

2. More than 25 cases reported in HIV-infected patients

3. Usually seen in patients on antiretroviral therapy but can occur without protease inhibitors

4. Mature, non-encapsulated fat tissue

5. No biochemical evidence of Cushing's syndrome

6. Spontaneous regression not reported; tends to recur after resection

B. Benign symmetrical lipomatosis

1. Described by Otto Madelung (1846); Launois and Bensaude (1898)

Symmetric accumulation of subcutaneous fat (esp neck and shoulder)

Confluent lipomas, not encapsulated, penetrate deeply into tissues

Insulin resistance, hyperlipidemia, hypertension, polyneuropathy

2. An increasing number of cases described in HIV-infected patients; to date, all on protease inhibitors

3. May overlap with buffalo hump

C. "Crix Belly" and "Protease Paunch"

1. Increasing abdominal girth, often associated with sensation of bloating, heartburn, and loss of fat in the extremities

2. Initially described in patients on indinavir but has occurred in patients on other protease inhibitors and in some who were never on protease inhibitors

3. Associated hyperlipidemia frequently seen

4. Increased visceral fat by abdominal CT in one study

D. Breast enlargement

1. Anecdotal reports in women on PI therapy

2. Can be painful and indurated

3. Often associated with thinning of buttocks and thighs

4. Reduction in breast size after discontinuing PI therapy

E. Lipodystrophy

1. Generalized (total) or regional (partial) absence of subcutaneous fat

2. Inherited lipodystrophy syndromes

Beradinelli-Selp (generalized)

Kobberling-Dunnigan (partial)

3. Acquired lipodystrophy syndromes

Lawrence (generalized)

Barraquer-Simons (partial)

4. Associated features include insulin resistance, hypertriglyceridemia, increased fat accumulation in unaffected areas, muscular hypertrophy

5. In HIV-infected patients, loss of subcutaneous fat in extremities and face, generally associated with increases in abdominal girth, insulin resistance, and hyperlipidemia