A study involving HIV-negative men has found that taking Kaletra can result in significant increases in some blood lipids, and suggests that the metabolic effects of protease inhibitors are drug-specific rather than a class effect. The study is published in the March 5th edition of AIDS.
Investigators from the University of California, San Francisco, examined the impact of four weeks of Kaletra on the lipid profiles of ten HIV-negative men. The investigators conducted the study in HIV-negative men because they wished to see if it was treatment with Kaletra rather than factors associated with HIV infection which were causing lipid abnormalities in HIV-positive patients taking Kaletra and other protease inhibitors.
The men had a mean age of 43.8 years and had a confirmed negative HIV test result. They were admitted as in-patients for five days and were placed on a carefully controlled diet to minimise dietary effects on the metabolism. They were then discharged and provided with four week's supply of Kaletra, and were instructed to eat their normal diet and engage in their normal exercise habits. After four weeks of Kaletra they were again admitted for blood tests and other examinations.
The investigators found that after four weeks of Kaletra treatment, fasting triglycerides increased three-fold (0.89 mmol/l at baseline to 1.63 mmol/l, p=0.007), that levels of VLDL cholesterol increased by a third (0.39mmol/l at baseline to 0.53mmol/l, p=0.05), and that free fatty acids (0.33mmol/l at baseline to 0.43mmol/l, p=0.001) also increased significantly.
No significant change was seen in LDL, HDL, or total cholesterol levels, nor in blood levels of fasting glucose levels, insulin, or insulin resistance. However, a two-hour oral glucose tolerance test revealed that there was an increase in glucose (p=0.05) and insulin (p=0.04) levels.
No changes in body shape were observed.
The investigators attribute the increase in triglycerides to ritonavir, and they note that increased VLDL production is thought to be involved in the mechanism associated with triglyceride elevation.
Elevated LDL cholesterol is seen in HIV-positive patients taking a protease inhibitor-containing HAART regimen. However, this was not seen in the ten HIV-negative men in this study, leading the investigators to speculate that increased LDL cholesterol in HIV-positive patients could be due to improving health or because of an interaction between HIV and HAART. The investigators admit to being uncertain if the mild impairment of glucose tolerance revealed by the two-hour glucose tolerance test was of any clinical significance.
The investigators also compared their results to a similar study involving the use of indinavir in HIV-negative individuals. They noted that indinavir had little effect on lipids in HIV-negative individuals, but significantly increased insulin resistance. They conclude that the metabolic effects of protease inhibitors appear to be “drug specific, not class specific.”
Further information on this website
Lopinavir - overview
Body fat and metabolic changes on treatment - menu
Lipodystrophy - factsheets
Grace AL et al. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS 18: 641 – 649, 2004.