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Et al. [14]. 2.three. Statistical Evaluation Each of the continuous variables were tested for normality with the Shapiro ilk test. The correspondence of every single parameter was evaluated having a typical or nonnormal distribution by means of the Kolmogorov mirnov test. Nonnormal variables were described as median values and interquartile variety (IQR), and categorical variables as numbers and percentages. Kruskal allis and Mann hitney tests have been adopted for differences in continuous variables involving seasons, thinking of a statistical significance with a twosided pvalue 0.05. Stepwise multivariate logistic regression analyses were performed to predict drug cutoff values (ETV). All tests have been performed with IBM SPSS Statistics for Windows v.26.0 (IBM Corp., Chicago, IL). 3. Final results Within this study, 4148 samples were regarded as; their traits are provided in Table 1. Percentages of therapy combinations are summarised in Table S1.Table 1. Characteristics in the described population.Qualities Number of sufferers (n) Age (years), median (range interquartile [IQR]) Male sex, n Female sex, n Weight, median [IQR] Height, median [IQR] Concomitant drugs, n Protonpump inhibitors, n Sufferers RTBDN Protein HEK 293 treated with nevirapine, n Patients treated with raltegravir, n Sufferers treated with darunavir, n HER3 Protein HEK 293 Individuals treated with ritonavir, n Patients treated with atazanavir, n Patients treated with etravirine, n Individuals treated with abacavir, n Patients treated with tenofovir, n Individuals treated with emtricitabine, n Sufferers treated with maraviroc, n Patients treated with lopinavir, n 4148 52 (475) 2846 (69 ) 1302 (31 ) 69 [588] 170 [16476] 1572 (37.9 ) 225 (5.4 ) 165 (four ) 518 (12.five ) 412 (9.9 ) 936 (22.six ) 721 (17.4 ) 102 (2.5 ) 137 (3.three ) 1612 (38.9 ) 1547 (37.three ) 340 (eight.2 ) 191 (4.6 )LPV, ETV and MVC concentrations showed a seasonal trend (p = 0.006, p = 0.002 and p = 0.001, respectively, Figure 1). In detail, LPV, ETV and MVC median concentrations are reported in Table 2. Particularly, MVC and ETV concentrations have been decrease in summer than in winter (p = 0.033 and p 0.001, respectively). However, LPV concentrations showed an opposite trend (p = 0.003, Figure two).Biomedicines 2021, 9,four ofFigure 1. Lopinavir, etravirine and maraviroc concentrations based on seasonal variation. Circles and stars indicate “out” values (small circle) and “far out” values (star).Biomedicines 2021, 9,5 ofFigure two. Lopinavir, etravirine and maraviroc levels in winter v. summer time. Circles and stars indicate “out” values (compact circle) and “far out” values (star). Table two. Lopinavir, etravirine and maraviroc median concentrations (ng/mL) in relation to seasonality.Season Winter Spring Summer time AutumnLopinavir Median Concentrations (ng/mL) [IQR] 5015 [2009541] 6829 [48391148.5] 7608 [4396012.5] 6906 [36780312]Etravirine Median Concentrations (ng/mL) [IQR] 562 [410133] 447 [234.560] 265 [17948.5] 602 [372.2554]Maraviroc Median Concentrations (ng/mL) [IQR] 178.5 [84.556.5] 135 [4273] 125 [5759.5] 99 [46.7540.25]Furthermore, our other aim was to evaluate if seasonality could possess a function in affecting the achievement of concentrations associated with drug efficacy or toxicity. ETV was the only ARV showing statistical significance (p 0.001) contemplating its therapeutic efficacy cutoff value of 300 ng/mL. Plasma samples with an ETV higher than 300 ng/mL were 37 (77.1 ) in winter but 11 (22.9 ) in summer season; samples with concentrations decrease than this cutoff had been six (30 ) in winter but 1.