There customer reviews were no significant associations between flu-like syndrome or depression and any of the genetic variants studied. Adverse gastrointestinal disturbances were associated with the ITPA rs1127354 polymorphism. Anemia was associated with the OAS1 rs2660 and the CTL4 rs231775 polymorphisms, and neutropenia and thrombocytopenia were associated with the polymorphism rs4969170 in the SOCS3 gene. Table 6 Association between the different types of adverse effects and the genetic variants assessed. We performed an univariate analysis of the association of the six categories of adverse effects defined and the clinical, virological and therapy variables that were assessed in the safety substudy (the variables used are detailed in Table 4). Among continuous variables, the significant associations observed were: flu-like syndrome with higher weight (71.

1��12.7 vs. 65.2��9 k.; p=0.02); depression with higher HIV plasma viral load (median 199 copies/mL, 25�C75% IQR 49�C298 vs. median 49 copies/mL, 25�C75% IQR 39�C199; p=0.045), neutropenia with lower CD4 T-cell count (median 508 cells/mL, 25�C75% IQR 340�C769 vs. median 591 cells/mL, 25�C75% IQR 497�C800; p=0.03) and thrombocytopenia with lower CD4 T-cell count (median 511 cells/mL, 25�C75% IQR 383�C704 vs. non neutropenic: median 611 cells/mL, 25�C75% IQR 473�C816; p=0.049). Among categoric variables, the only significant associations observed were: neutropenia with pegIFN�� 2a vs. 2b (OR 2.6, 95CI 1.2�C5.7, p=0.01), and with female vs. male gender (OR 2.7, 95%CI 1.1�C6.4, p=0.02); and thrombocytopenia with pegIFN�� 2a vs.

2b (OR 2.9, 95%CI 1.3�C6.3, p=0.008). For multivariate analyses, we constructed a logistic regression model which included the adverse effects categories that were associated with more than one clinical, analytical, virological or genetic variable in the univariate analysis. The only adverse effects that fulfilled these criteria were neutropenia and thrombocytopenia. With respect to neutropenia we constructed a multivariate regression model which included the following variables: gender, type of pegIFN�� prescribed, CD4 cell count stratified in two categories (��350 and >350 cells/mL) and SOCS3 rs4969170 genotype. The use of pegIFN�� 2a and CD4 cell count ��350 cells/mL was associated with greater risk of neutropenia while carriers of the SOCS3 rs4969170 AG genotype had significantly lower risk of neutropenia.

Regarding thrombocytopenia, the model included the type of pegIFN�� prescribed, stratified CD4 cell count, and SOCS3 rs4969170 Brefeldin_A genotype. Patients treated with pegIFN�� 2a had significantly higher risk of thrombocytopenia, and carriers of the SOCS3 rs4969170 AA genotype had significantly lower risk of thrombocytopenia (Table 7). Table 7 Independent predicitive factors of adverse effects.

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