PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy.

OBJECTIVES: To analyze whether peroxisome proliferator-activated receptor gamma (PPARγ2) rs1801282 (Pro12Ala) polymorphism is associated with the response to pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV treatment. DESIGN: Retrospective follow-up study. METHODS: Two hundred eighty-five naive patients, who started HCV-treatment, were genotyped for PPARγ2 and interleukin 28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment. RESULTS: The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000 IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F < 2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPARγ2 rs1801282 CG/GG genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPARγ2 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves was 0.766 ± 0.028. CONCLUSIONS: The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with increased odds for achieving SVR in HIV/HCV-coinfected patients on HCV treatment.

Soluble markers of inflammation are associated with Framingham scores in HIV-infected patients on suppressive antiretroviral therapy.

OBJECTIVE: To evaluate the association between biomarkers of inflammation and endothelial dysfunction and Framingham scores (FS) for risk of coronary heart disease (FS-CHD), stroke (FS-Stroke) or any cardiovascular event (FS-CVE) in HIV-infected on suppressive highly active antiretroviral therapy (HAART). METHODS: A cross-sectional study was conducted in 73 HIV-infected patients and 23 healthy controls. Inflammatory molecules and endothelial dysfunction markers were measured using a multiplex immunoassay (plasminogen activator inhibitor type 1 (PAI-1), soluble TNF receptor type 1 (sTNF-R1), soluble CD40 ligand (sCD40L), soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1). Outcome variables were FS-CHD ≥10%, FS-Stroke ≥5% and FS-CVE ≥10%. RESULTS: Significant differences (p < 0.05) were found comparing controls and HIV patients for PAI-1 (5.4 vs. 13.5 ng/dL), sTNF-R1 (0.85 vs. 1.09 ng/dL), sICAM-1 (529 vs. 858 ng/dL), sE-selectin (73.7 vs. 120 ng/dL), sP-selectin (676 vs. 1511 ng/dL) sCD40L (76 vs. 307 ng/dL), FS-CHD (4% vs. 7.8% L), FS-Stroke (2% vs. 2.8%) and FS-CVE (5% vs. 11%). In HIV-infected patients, the adjusted logistic regression analysis revealed that sTNF-R1 levels were significantly associated with increased FS-CHD>10% (OR: 11.51 (95% CI: 1.14; 115.84); p = 0.038) and FS-CVE (OR: 12.41 (95% CI: 1.25; 123.23); p = 0.031). CONCLUSIONS: HIV-infected patients show higher levels of soluble inflammatory and endothelial dysfunction markers than controls and have a two-fold increased FS of presenting coronary heart disease, stroke or cardiovascular events at 10 years. Furthermore, sTNF-R1 displayed the best association with FS of coronary heart disease and any cardiovascular event in our patients.