Browsing by Author "Owen, Andrew (7202052634)"

BACKGROUND:: Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV. METHODS:: Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10-14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann-Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis. RESULTS:: Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460-3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160-2480) ng/mL; GT (n = 30), 3230 (range, 2790-3670) ng/mL; and TT (n = 2), 10,700 (range, 6170-15,300) ng/mL (P = 2.0 × 10). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [β = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [β = -464 (-1250 to -43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations. CONCLUSIONS:: The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time. © 2014 by Lippincott Williams & Wilkins.

BACKGROUND:: Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV. METHODS:: Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10-14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann-Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis. RESULTS:: Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460-3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160-2480) ng/mL; GT (n = 30), 3230 (range, 2790-3670) ng/mL; and TT (n = 2), 10,700 (range, 6170-15,300) ng/mL (P = 2.0 × 10). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [β = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [β = -464 (-1250 to -43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations. CONCLUSIONS:: The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time. © 2014 by Lippincott Williams & Wilkins.

Background and Objectives: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections present significant public health challenges worldwide. The management of these infections is complicated by the need for antiviral and antiretroviral therapies, which are influenced by drug metabolism mediated by metabolic enzymes and transporters. This study focuses on the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in patients with HIV, HCV, and HIV/HCV co-infection, aiming to assess their potential association with the choice of therapy, patohistological and clinical parameters of liver damage such as the stage of liver fibrosis, serum levels of ALT and AST, as well as the grade of liver inflammation and other available biochemical parameters. Materials and Methods: The study included 54 patients who underwent liver biopsy, divided into HIV-infected, HCV-infected, and co-infected groups. The mRNA levels of CYP2B6, CYP3A4, and ABCB1 was quantified and compared between the groups, along with the analysis of liver fibrosis and inflammation levels. Results: The results indicated a significant increase in CYP2B6 mRNA levels in co-infected patients, a significant association with the presence of HIV infection with an increase in CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression was observed in patients using lamivudine. Conclusions: This study provides insight into gene expression of CYP2B6 CYP3A4, and ABCB1 in HIV, HCV, and HIV/HCV co-infected patients. The absence of correlation with liver damage, inflammation, and specific treatment interventions emphasises the need for additional research to elucidate the complex interplay between gene expression, viral co-infection, liver pathology, and therapeutic responses in these particular patients population. © 2023 by the authors.

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 (Ctrough) in Serbian patients. Methods: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough 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 Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318–7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300–6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949–4072 ng/mL) (P =.005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548–8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300–6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361–5233 ng/mL) (P =.007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855–6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088–8063 ng/mL) and C-homozygotes (LPV median Ctrough = 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 Ctrough (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 Ctrough in Caucasian HIV/AIDS patients. © 2020 The British Pharmacological Society

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 (Ctrough) in Serbian patients. Methods: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough 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 Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318–7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300–6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949–4072 ng/mL) (P =.005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548–8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300–6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361–5233 ng/mL) (P =.007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855–6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088–8063 ng/mL) and C-homozygotes (LPV median Ctrough = 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 Ctrough (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 Ctrough in Caucasian HIV/AIDS patients. © 2020 The British Pharmacological Society