Aim: Lopinavir (LPV) is a potent protease inhibitor used in combination with low doses of ritonavir in the treatment of HIV-infected patients. LPV pharmacokinetics is characterized by a large interindividual variability requiring the use of therapeutic drug monitoring in different clinical situations. While the sources of this variability are still unknown, several genetic polymorphisms in biotransformation enzymes or transporter proteins involved in the metabolism and/or the distribution of LPV appear as good candidates. Therefore, the aim of the present study was to investigate the influence of selected genetic polymorphisms on LPV trough plasma concentrations ([LPV]_Cmin), LPV concentrations in peripheral blood mononuclear cells ([LPV]_CC) and the LPV accumulation ratio ([LPV]_CC:[LPV]_Cmin). Materials & methods: A total of 53 patients receiving Kaletra^® (Abbott Laboratories, IL, USA) (LPV+ritonavir) were genotyped for 14 different polymorphisms in biotransformation enzymes and transporter proteins. [LPV]_Cmin, [LPV]_CC and [LPV]_CC:[LPV]_Cmin were compared according to the patient’s genotypes. Results & conclusion: The 4544G>A (rs8187710)polymorphism in ABCC2 was associated with a higher accumulation of LPV in peripheral blood mononuclear cells of HIV-treated patients. As already observed in previous studies, ABCB1 or CYP3A5 polymorphisms had no impact on [LPV]_Cmin and we did not detect any influence of these polymorphisms on [LPV]_CC and its accumulation in mononuclear cells. In conclusion, this pilot study suggests, for the first time, that the 4544G>A polymorphism in ABCC2 could explain a significant part of the interindividual variability in LPV pharmacokinetics. Further investigations are needed to confirm this association and to explore its real pharmacodynamic impact.