Background

1. Lopinavir plasma concentrations and lipid elevation patterns in patients on lopinavir/ritonavir-containing regimens. M Boffito1,2, S Bonora2, A Sinicco2, R Raiteri2, PG Hoggard1, SH Khoo1, DJ Back1, G Di Perri2 1University of Liverpool, Liverpool, UK; 2University of Torino, Torino, Italy CORRESPONDENCE: MARTA BOFFITO martalbb@hotmail.com n MEDIAN AGE (range) GENDER (F/M) RISK FACTOR (SEX/IVDU) HCV (+/-) 30 41 (37-64) 3/25 10/30 21/9 • Background Hypertrigliceridaemia is common in patients with HIV, especially those taking protease inhibitors (PIs) or with lipodystrophy. Although, plasma PI concentrations have been shown to be correlated with virological response there is no clear link between PI concentrations and toxicity, especially long-term side effects, such as lipid metabolism disregulation. Aim To investigate the relationship between lopinavir (LPV) plasma levels and changes in plasma triglycerides (TG), total cholesterol (TC), and high and low density lipoprotein cholesterol (HDL, LDL) in HIV-infected patients on LPV/ritonavir (r). Patients and methods Thirty HIV+ patients (Table 1) starting LPV/r + 2 nucleoside reverse transcriptase inhibitors have been enrolled and followed for 12 months. CD4+ cells, HIV-RNA, glucose, TG, TC, HDL-C and LDL-C plasma concentrations were assessed at baseline (0) and 1, 3, 6 and 12 months after LPV/r initiation. LPV trough concentrations in plasma (Ctrough) were measured by HPLC-MS/MS at 1, 3, 6 and 12 months after LPV/r initiation. Correlations between LPV Ctrough and lipid plasma levels were investigated using linear regression and Pearson’s correlation. Table 2: Tryglicerides and total cholesterol concentrations: comparison between the 30 patients enrolled and the 24 who ended the follow-up period. Figure 1: Tryglicerides and total cholesterol concentrations over the 12 month follow-up period Table 1: Demographics of the 30 patients enrolled in the study Results Twenty-four patients reached 12 month follow-up, while 6/30 (20%) had a major increase in TG plasma levels (to  400 mg/dL) during the first 3 months of LPV/r therapy and started lipid regulating treatment (gemfibrozil 600 mg BID, n = 4; fenofibrate 200 mg QD, n = 2). All subjects showed the expected decrease in plasma lipids when treated. Plasma TG levels showed a transient increase over the 12 month follow-up: they increased during the first 3 months of LPV/r therapy before decreasing at month 6 and 12, without reaching statistical significance (p > 0.05, ANOVA). No correlation was observed between LPV Ctrough and TG plasma concentrations, TG increases from baseline, TC, HDL-C and LDL-C. This was confirmed in both group of patients: the 30 enrolled and the 24 who completed the study. Moreover, comparing the 6 patients who reached a TG level > 400 mg/dL with the 24 who completed the study, no differences were observed in median LPV Ctrough (6274 vs 6428 ng/mL). Figure 2: Linear regression between tryglicerides and LPV Ctrough Conclusions A transient increase in TG was observed in this cohort of antiretroviral drug experienced HIV-patients. However, no correlation between LPV Ctrough and lipid elevations was observed, suggesting lipid metabolism alterations may not depend on drug plasma concentrations. Interestingly, our results were not in accordance with other studies performed in different countries, in similar number of patients and with similar follow-up times, which showed a significant relationship between LPV plasma concentrations and hypertriglyceridaemia. • Further studies are warranted to clarify the impact of LPV plasma concentrations on lipid elevation.