Browsing by Author "Dimitrijević, Božana (59097555200)"

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

Background The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy. Methods Cross-sectional study of 66 HIV/AIDS patients, all Caucasians. Serum levels of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10) were measured using Cytokine-Array-1 on Evidence Investigator, Biochip Array Technology. The associations between interleukins and anthropometric and metabolic variables were estimated by Spearman-correlation. Analysis of covariance with bootstrapping method (ACBM) was used to examine relationship between interleukins and lipodystrophy categories adjusted for confounding variables. Results The lipodystrophy was observed in 29 (44%) patients, while 15 (52%) had lipoatrophy, 4 (14%) lipohypertrophy and 10 (34%) patients had mixed fat redistribution. There were 37 (56%) patients without lipodystrophy. Significantly lower levels of IL-4 and IL-10 were observed in lipodystrophy vs. non-lipodystrophy (p = 0.008; p = 0.027, respectively). No differences were found relating IL-1α, IL-1β, IL-2, IL-6 and IL-8 levels in lipodystrophy vs. non-lipodystrophy. In patient subgroup with lipoatrophy, significantly lower levels of IL-4 and IL-10 were found when compared to non-lipodystrophy (p = 0.043; p = 0.031, respectively). In lipohypertrophy subgroup significantly lower levels of IL-4 were found when compared to non-lipodystrophy (p = 0.003). In order to estimate the correlation of IL-4 and IL-10 and the presence of lipodystrophy, ACBM showed that correlation of IL-4 levels in patients with lipodystrophy remains statistically significant (p = 0.004) in all types of lipodystrophy: lipoatrophy, lipohypertrophy and mix-fat-redistribution (p = 0.027; p = 0.009; p = 0.017, respectively) after adjustment for age, BMI. Conclusions IL-4 and IL-10 levels were significantly lower in lipodystrophy vs. non-lipodystrophy. According to our knowledge, we showed for the first time significant correlation between IL-4 levels and lipodystrophy development in HIV/AIDS patients. © 2017

Background The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy. Methods Cross-sectional study of 66 HIV/AIDS patients, all Caucasians. Serum levels of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10) were measured using Cytokine-Array-1 on Evidence Investigator, Biochip Array Technology. The associations between interleukins and anthropometric and metabolic variables were estimated by Spearman-correlation. Analysis of covariance with bootstrapping method (ACBM) was used to examine relationship between interleukins and lipodystrophy categories adjusted for confounding variables. Results The lipodystrophy was observed in 29 (44%) patients, while 15 (52%) had lipoatrophy, 4 (14%) lipohypertrophy and 10 (34%) patients had mixed fat redistribution. There were 37 (56%) patients without lipodystrophy. Significantly lower levels of IL-4 and IL-10 were observed in lipodystrophy vs. non-lipodystrophy (p = 0.008; p = 0.027, respectively). No differences were found relating IL-1α, IL-1β, IL-2, IL-6 and IL-8 levels in lipodystrophy vs. non-lipodystrophy. In patient subgroup with lipoatrophy, significantly lower levels of IL-4 and IL-10 were found when compared to non-lipodystrophy (p = 0.043; p = 0.031, respectively). In lipohypertrophy subgroup significantly lower levels of IL-4 were found when compared to non-lipodystrophy (p = 0.003). In order to estimate the correlation of IL-4 and IL-10 and the presence of lipodystrophy, ACBM showed that correlation of IL-4 levels in patients with lipodystrophy remains statistically significant (p = 0.004) in all types of lipodystrophy: lipoatrophy, lipohypertrophy and mix-fat-redistribution (p = 0.027; p = 0.009; p = 0.017, respectively) after adjustment for age, BMI. Conclusions IL-4 and IL-10 levels were significantly lower in lipodystrophy vs. non-lipodystrophy. According to our knowledge, we showed for the first time significant correlation between IL-4 levels and lipodystrophy development in HIV/AIDS patients. © 2017