Aims: We present a genetic association study in 106 European HIV-infected individuals aimed at identifying and confirming polymorphisms that have a significant influence on toxicity derived from treatment with lopinavir/ritonavir (LPV/r). Patients & methods: Genotyping was performed by matrix-assisted laser desorption/ionization-time of flight and KASPar^® (KBiosciences, Hoddesdon, UK); LPV/r plasma concentrations were quantified using HPLC with an UV detection system and the pharmacokinetic parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with PASW Statistics 18 (SPSS Inc., IL, USA) and R for Windows (Microsoft, WA, USA). Results: Suggestive relationships have been established between lipid plasma levels and total bilirubin and SNPs in CETP, MCP1, ABCC2, LEP and SLCO1B3 genes and between diarrhea and SNPs in IL6 gene. Conclusion: Replication analysis should confirm the novel results obtained in this study prior to its application in the clinical practice to achieve a safer LPV/r-based combined antiretroviral therapy.