Complications in patients with HIV

• Glucose homeostasis: PI therapy appears to directly affect glucose homeostasis, and ddI may be a contributing factor.
• Dyslipidemia: HIV infection (without therapy) is associated with decreased HDL followed by decreases in LDL and then increases in triglyceride levels. More recent studies show that PI-containing regimens are associated with increased levels of triglycerides, total and LDL cholesterol and lipoprotein A.

Management

• General: Interventions should be directed toward specific abnormalities. Discontinuing antiretroviral therapy should be discouraged as a method to reverse body shape abnormalities because this does not seem to work. The following are changes that are directed primarily at improving lipid levels and the risk of CAD.
• Diet: The prior recommendation of a low fat, high carbohydrate diet for weight loss and reduction in triglycerides to reduce CAD risk may actually be harmful. A more recent recommendation is moderate fat and substitution of monosaturated for saturated fatty acids to reduce lipogenesis and decrease insulin resistance. This has not been studied in HIV infected patients.
• Exercise: Established merit for reducing risk for CAD and diabetes with no adverse effects on HIV.
• Metformin: Appears to reverse changes in glucose homeostasis and body shape changes. One study showed reduction in weight, blood pressure, fasting insulin levels, glucose levels, and waist circumference [JAMA 2000;284:472]. Careful monitoring is necessary due to the risk of lactic acidosis, especially with renal dysfunction [Diabetes Care 1997;20:925].
• Glitazones: These drugs improve glucose uptake and reduce glucose levels, but have no effect on insulin sensitivity, lipid profiles or fat distribution. Pioglitazone induces CYP 3A4, but rosiglitazone does not.
• Statins: The recommendation is to adhere to the NCEP guidelines for indications, but pravastatin is the preferred statin; atorvastatin and simvastatin may be used with caution or with reduced doses.
• Fibrates: These drugs reduce triglycerides and slightly reduce cholesterol levels, but they are metabolized by the CYP 3A4 pathway.
• Switch therapy: Data are limited, but there appears to be evidence that changing PI therapy to triple NRTI or to a NNRTI-based regimen will improve metabolic parameters, but not improve body-shape changes.
• Cosmetic surgery: May improve appearance, but long-term effects are not known. Liposuction is considered dangerous with HIV infection because abdominal adiposity is visceral rather than subcutaneous.
• Anabolic steroids: Testosterone may reduce visceral fat, lower cholesterol and reduce blood pressure, but studies supporting use for treating or preventing HIV-associated lipodystrophy are limited. Disadvantages of anabolic steroids are the reduced HDL, possible hepatotoxicity and risk of prostatic cancer.
• Growth hormone: Initial studies show this drug at 6 mg/day for 12 weeks significantly reduces BMI, waist-hip ratio, triglyceride and total cholesterol levels, but increases fasting glucose. Preliminary data for growth hormone at 4 mg every other day or 3 mg/day may be effective in reducing buffalo hump and abdominal girth.

Monitoring

• Questionnaire to screen for risk factors.
• Charting of weight, blood pressure, waist circumference, glucose levels and fasting lipid levels.
• Diabetes: Random glucose test or fasting glucose.
• Lipid levels: Fasting lipid panel at baseline and repeated every 6-12 months and with any change in therapy. Treatment is recommended if the triglyceride exceeds 400 mg/dL and for cholesterol levels above 200 mg/dL.