Various treatments of fat redistribution syndrome-associated lipid disorders have been reported. A study from Paris showed moderate improvement in hypertriglyceridemia with dietary intervention comparable to that recommended for non-HIV associated hypertriglyceridemia. These patients predominantly had a pre-intervention increase in caloric intake of sugars and alcohol. Indeed controlling this intake was the major factor in controlling the hypertriglyceridemia. Another study from France used atorvastatin (lipitor) in 12 patients on HAART with protease inhibitors. After 60 days of therapy at 10 mg/day statistically significant declines in total and LDL cholesterol were reported; neither triglyceride nor HDL levels changed. Tolerance was excellent, but there was a possible pharmacokinetic interaction with atorvastatin on saquinavir (related to cytochrome P450).
The other recognized metabolic component of fat redistribution syndrome is insulin resistance (IR) which leads to hyperglycemia and even frank diabetes mellitus in some. IR is commonly seen in catabolic states as well as obesity but seems to be related in HIV infection to HAART. Though some earlier studies raised the possibility of a direct or indirect effect of HIV-infection itself on glucose metabolism, HAART seems to be the major factor. Mulligan of San Francisco previously reported on 20 patients studied before and after initiation of antiretroviral therapy and demonstrated the association of protease inhibitors with modest elevations of blood sugar and elevated insulin levels (a sign of insulin resistance). The treatment of insulin-resistance associated diabetes typically includes diet modification and exercise. Drug therapy includes insulin, other hypoglycemics such as sulfonylureas and a relatively new class of drugs called insulin sensitizers. These drugs represented by troglitazone (rezulin) and metformin (glucophage) are available in the USA (and elsewhere) for the treatment of diabetes. Dr. Ravi Walli from Munich used troglitazone (400 mg/day) in 6 patients with HAART-associated diabetes in a 3-month pilot study. 4 showed evidence of insulin sensitization with improved glycemic control. He did caution about the possibility of hepatotoxicity; indeed the FDA has recently re-reviewed the safety of this drug because of reports of fatalities associated with troglitazone.
Metformin may be a better alternative because its potentially serious toxicity, namely lactic acidosis, is quite rare and unlikely to occur in this setting of nonacidotic (non-insulin dependent) diabetes. Dr. Thierry Saint Marc from Lyons, France used metformin (850mg tid) in 16 male patients with HAART and at least one PI. After 8 weeks a significant lowering of insulin levels, triglycerides, glucose as well as decreased body fat, visceral adipose tissue and waist-hip ratio was seen. 13 additional patients served as controls and did not receive drug therapy and showed the classical signs of insulin resistance: elevated blood glucose, insulin levels, C-peptide and increases in abdominal fat. 2/16 patients stopped metformin due to gastrointestinal adverse effects; 6-month therapy was associated with worsening adherence (due to pill burden). He concluded that hyperinsulinemia is detectable before overt diabetes, that metabolic effects on glucose occur within 8 weeks of initiation of PI therapy and that metformin reverses some of these abnormalities. Metformin should be studied further in treatment of HAART-associated insulin resistance and hyperglycemia.