526 Relation between Lopinavir Plasma Blood Concentrations and Hypertriglyceridemia in Naïve and Protease Inhibitors-experienced Patients A. Calboreanu1, J. Dimet2, J.M. Treluyer2, S. Abad1, L. Pecqueux1, A. Krivine2, D. Sicard1, D. Salmon-Ceron*1 1Internal Med Dept, Cochin Hosp, Paris, France and 2Cochin Hosp, Paris, France
Background: In HAART treated patients (pts), a correlation has been found between plasma blood levels of several protease inhibitors (PI) and the occurrence of their side effects.
Objective: To evaluate whether there is a relationship between lopinavir (LPV) plasma concentrations and the occurrence of lipid abnormalities in lopinavir/ritonavir treated pts.
Method: We performed a prospective open-labeled study in pts initiating LPV as a part of their HAART regimen. Residual plasma concentrations (Cres) of LPV were measured at mo 1 (M1) and once between mos 3 and 6 (M3/6). Fasting cholesterol (CHOL) and triglycerides (TG) were measured at mo 1 and every 3 mos.
Results: As of October 2002, 29 pts have been followed for a mean of 5.6 mos, of which 8 were PI-naïve (baseline median CD4: 238/mm3, median viral load (VL): 40,725 cop/mL) and 21 were PI-experienced (baseline CD4: 319/mm3, median VL: 8,600 cop/mL). At baseline, 9 pts were hypertriglyceridemic (> 2.1 mmol/L) and none hypercholesterolemic (> 7.7 mmol/L). Thirteen (13) of 20 pts with normal TG at baseline developed an hypertriglyceridemia and 8 of 28 with normal CHOL developed an hypercholesterolemia. Median levels of TG were 1.65, 2.49, 2.26 mmol/L at baseline, mo 1 and mos 3/6, respectively. Median Cres of LPV were 7.05 mg/l (1.11-11.8) at M1 and 7.19 mg/l (0.29-13.7) at M3/6. No correlation was found between Cres of LPV and VL decrease at any time. Mean increases of TG were significantly higher (p < 0.01) in pts who had Cres of LPV higher than the median (+1.07 mmol/lfor those with mean LPV Cres of 9.3 mg/L) than in pts with LPV Cres lower than the median (+0.38 mmol/l for those with mean LPV Cres of 4.18 mg/l). This trend was not significant at M3/6. The percentage of pts with dyslipidemia did not differ between naïve and PI-experienced pts.
Conclusion: These results suggest a relationship between residual plasma concentrations of LPV and occurrence of lipid abnormalities. Larger prospective studies need to be done in order to assess whether pharmacological monitoring is useful to adapt high lopinavir concentrations, thus possibly diminishing their metabolic side effects.
