Abstract
AIMS: Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (C(trough) ) in Serbian patients. METHODS: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV C(trough) was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis. RESULTS: The overall mean (SD) LPV C(trough) was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median C(trough) = 6072 ng/mL, interquartile range (IQR) = 4318-7617 ng/mL), CA (LPV median C(trough) = 4987 ng/mL, IQR = 4300-6295 ng/mL) and AA (LPV median C(trough) = 3648 ng/mL, IQR = 1949-4072 ng/mL) (P = .005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median C(trough) = 6027 ng/mL, IQR =4548-8250 ng/mL), CT (LPV median C(trough) = 5553 ng/mL, IQR = 4300-6888 ng/mL) and TT (LPV median C(trough) = 4408 ng/mL, IQR = 3361-5233 ng/mL) (P = .007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median C(trough) = 5434 ng/mL, IQR = 3855-6830 ng/mL), heterozygotes (LPV median C(trough) = 6707 ng/mL, IQR = 5088-8063 ng/mL) and C-homozygotes (LPV median C(trough) = 13906 ng/mL, IQR = 12946-14866 ng/mL) was observed (P = .002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV C(trough) (β = 2834.5 [1442-4226.9] ng/mL [P = .001]). CONCLUSIONS: Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV C(trough) in Caucasian HIV/AIDS patients.