Does Stopping PI Reverse Lipodystrophy?

This study compared patients who had lipodystrophy and either continued on a PI regimen or stopped their PI regimen (they either took a treatment break or switched to a non-PI regimen). Cholesterol and LDL cholesterol (bad cholesterol) were the only things to improve after 12 months follow-up. In the patients staying on the PI: the weight and mid thigh circumference decreased, the hip circumference increased, and the levels of glucose, Lp(a), and fbg increased. The levels of cholesterol and LDL-Cholesterol decreased in both the patients who switched to non-PI regimen and in the patients who had a treatment pause.

Is hyperlipidemia the only cardiovascular risk factor that normalises when discontinuing protease inhibitors?
K. Koppel, G. Bratt, B. Lund, E.-L. Fredriksson and E. Sandström
Venhälsan Gay Men’s Health Clinic at Stockholm Söder Hospital, 118 83 Stockholm, Sweden

Purpose of the study:
To follow the metabolic effects of protease inhibitor (PI) containing highly active antiretroviral treatment (HAART) longitudinally.

292 patients with a mean age of 42 years, HIV-1 infected for a mean of 99 months of whom 53 had prior AIDS, were followed for 12 months regarding weight, body measures, plasma levels of triglycerides (TG), cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), lipo-protein (a) [Lp(a)], glucose, insulin, plasminogen activator inhibitor 1 (PAI-1) and fibrinogen (fbg). 230 patients were on PI-HAART since 21 months, while 62 were treatment naïve. The patients who discontinued PI-HAART during the study period had an estimated PI-free observation time of 6 months.

Summary of results:
At study start the PI-HAART patients had lower hip circumference (P < 0.05), higher levels of TG (P < 0.001), cholesterol (P < 0.001), LDL-C (P < 0.001), insulin (P < 0.01), Lp(a) (P < 0.05), PAI-1 (P < 0.001) and fbg (P < 0.001) as compared to the treatment naïve patients. After 12 months, 6/62 had started PI-HAART, 186/230 had continued PI-HAART and 44/230 on PI-HAART had discontinued PI and were either on a non-PI containing regimen (n =25) or had a treatment pause (n =19). Thus two main groups were identified: A) PI-HAART PI-HAART (n =186) and B) PI-HAART stopped PI (n =44). In group A) the weight and mid thigh circumference decreased (P < 0.05), the hip cir-cumference increased (P < 0.05), and the levels of glucose (P < 0.001), Lp(a) (P < 0.001) and fbg increased (P < 0.001). In group B) the levels of cholesterol (P < 0.001) and LDL-C decreased (P < 0.01). The levels of cholesterol and LDL-C decreased in both the patients who switched to non-PI HAART (P < 0.05; P < 0.05) and in the patients who had a treatment pause (P < 0.01; P < 0.05).

In the group continuing PI-HAART, glucose, Lp(a) and fibrino-gen levels continued to increase during the 12 months observation time. The weight decreased, possibly due to subcutaneous fat loss. However, after stopping PI only cholesterol and LDL-C tended to normalise. Thus the plasma hypercholesterolemia, i.e. the increased cholesterol and LDL-cholesterol, seem to be reversible when discontinuing PI treatment whereas the increased levels of Lp(a), insulin, PAI-1 and fbg might persist.