10th Conference on Retroviruses and Opportunistic Infections Boston, MA USA - February 10 -14, 2003

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 748
G. A. Lee¹ , T. Seneviratne¹, M. A. Noor¹, J. C. Lo², J-M. Schwarz³, K. Mulligan², M. Schambelan², C. Grunfeld^4
1Univ of California at San Francisco; ²San Francisco Gen Hosp, CA; ³Univ of California at Berkeley; and ⁴San Francisco Dept of Veterans Affairs Med Ctr, CA

BACKGROUND: HIV protease inhibitor (PI) therapy has been associated with hyperglycemia, hyperlipidemia, and changes in body composition, but whether the changes are direct effects of the drugs or due to changes in disease status is unclear. Previously, it has been shown that in healthy, HIV-seronegative subjects, ritonavir elevates triglyceride and VLDL levels while lowering HDL levels, whereas indinavir induces insulin resistance without changing lipid levels.

METHODS: To differentiate the direct effects of lopinavir/ritonavir from those related to HIV infection itself, 400 mg lopinavir/100 mg ritonavir was given twice daily to 10 healthy HIV-seronegative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance (oGTT), insulin sensitivity by euglycemic, hyperinsulinemic clamp, and body composition were determined before and after 4 wks of lopinavir/ritonavir.

RESULTS: Fasting triglycerides (0.89 ± 0.15 vs 1.63 ± 0.36 mmol/l; p = 0.007) and free fatty acid levels (0.33 ± 0.04 vs 0.43 ± 0.06 mmol/l; p = 0.001) increased after 4 wks of treatment with lopinavir/ritonavir. There was a trend towards an increase of VLDL (15.1 ± 2.6 vs 20 ± 3.3 mg/dL; p = 0.054). There was no change in fasting LDL, HDL, IDL, Lp(a), or total cholesterol levels. There were no changes in HDL or LDL subspecies. During oGTT, 2 hrs glucose (4.6 ± 0.3 vs 5.9 ± 0.6 mmol/l; p = 0.05) and insulin (99.64 ± 21.9 vs 187.9 ± 48.4 pmol/l; p = 0.04) increased significantly. FFA were suppressed during the oGTT on lopinavir/ritonavir. AUC glucose levels (16.9 ± 0.8 vs 18.6 ± 1.4 mmolh/l; p = 0.077) increased slightly but fasting glucose and insulin levels remained unchanged. Insulin mediated glucose disposal rate per unit of insulin (M/I) during the clamp did not change after treatment. During the 4-wk study, there were no significant changes in weight (78.6 ± 3.8 vs 78.2 ± 3.8; p = 0 .21), percentage body fat, or adipose tissue (either visceral or subcutaneous) by computed tomography.

CONCLUSIONS: Treatment with 4 wks of lopinavir/ritonavir in HIV-seronegative men causes an increase in triglycerides and free fatty acids. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 hrs, but there is no significant change in insulin mediated glucose disposal rate by euglycemic, hyperinsulinemic clamp. These data indicate that each individual PI must be studied to determine its specific metabolic profile.

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