The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men.

AIMS To investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388A -> G, 463C -> A, 521T -> C) and lopinavir/ritonavir plasma concentrations. METHODS The study included 99 human immunodeficiency virus-infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography-tandem mass spectrometry. Genotyping of SLCO1B1388A -> G, 463C -> A and 521T -> C polymorphisms was performed by allelic discrimination using real-time polymerase chain reaction. RESULTS The trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521T -> C genotypes (P = 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P = 0.02). Carriers of the 521 C allele display significantly higher lopinavir plasma concentrations relative to the wild-type TT genotype (P = 0.03). CONCLUSIONS Reduced uptake of lopinavir by hepatocytes in carriers of the 521 C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.