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Hepatitis C virus ( HCV) infection is associated with insulin resistance ( IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B ( IL28B) and interleukin 28 receptor alpha ( IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate® assay. IR was defined as homeostatic model assessment ( HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% ( n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients ( P = 0.024), as well as the subgroups of patients with significant fibrosis ( P = 0.047) and infected with HCV genotype 3 ( P = 0.024). Additionally, rs10903035 AA was significantly associated with IR ( HOMA ≥3.00) in all patients (adjusted odds ratio ( aOR) = 2.02; P = 0.034), in patients with significant fibrosis ( aOR = 2.86; P = 0.039) and HCV genotype 3 patients ( aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype. [ABSTRACT FROM AUTHOR]

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate® assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment. [ABSTRACT FROM AUTHOR]

Objective To assess the antiviral efficacy and safety of switching from a protease inhibitor (PI) to nevirapine in patients with long-term HIV-1 RNA suppression on PI-containing regimens, and to assess its influence in the adherence to treatment. Methods In an open-label multicentre study, 160 HIV-infected patients with undetectable viral load for at least 6 months on a PI-containing regimen were randomized to either continue with their PI regimen ( n=79) or replace PI with nevirapine ( n=81). Clinical assessment included plasma HIV-1 RNA, blood chemistry, haematology, lymphocyte counts and adverse events reports. Adherence to treatment and lipodystrophy syndrome were assessed by patient self-reporting. Results Treatment efficacy was equivalent in the two arms, for patients with viral loads either above or below 100 000 HIV-1 RNA copies/mL. The increase in CD4 cell count was significant in both arms ( P<0.00001) but the average CD4 cell count at 48 weeks was slightly higher in the nevirapine arm (596 vs. 569; P=0.1588). The number of patients with severe hypertriglyceridaemia (>400 mg/dL) after 48 weeks of treatment decreased in the nevirapine arm (from 11 to six), but increased in the PI arm (from four to 11) and led to treatment discontinuation in two patients. Lipodystrophy changes increased in 15% of patients in the PI arm but decreased in 4% of patients in the nevirapine arm. Finally, although adherence was similar in the two arms, patients reported that it required significantly less effort to stay on treatment in the nevirapine arm. Conclusions The results indicate that switching from PI to nevirapine is as effective as continuing with PI for maintaining viral control, even in patients with baseline viral load above 100 000 copies/mL. In addition, reductions in hypertriglyceridaemia and lipodystrophy and in the effort required to stay on treatment were observed. [ABSTRACT FROM AUTHOR]