Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV-/HCV-coinfected patients: the role of metabolic factors and elevated GGT levels

Abstract

Evaluation of metabolic factors and elevated γ-glutamyltransferase (GGT) levels as independent predictors of treatment failure in a thoroughly documented cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients treated with pegylated interferon-α-2a plus ribavirin (PEGIFN+RBV) at the Medical University of Vienna within a prospective trial were included in this study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS cohorts were included as a validation cohort. Advanced liver fibrosis, GGT elevation, insulin resistance (IR) and low CD4+nadir were defined as METAVIR F3/F4, GGT levels >1.5× sex-specific upper limit of normal, homoeostasis model assessment of insulin resistance >2 and CD4+nadir <350cells/μL, respectively. HCV-genotype 1/4 (OR26.3; P=0.006), advanced liver fibrosis (OR20.2; P=0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P=0.02) and GGT elevation (OR7.97; P=0.012) were independent predictors of treatment failure, while both IR (OR3.51; P=0.106) and low CD4+nadir (OR2.64; P=0.263) were not independently associated with treatment failure. A statistically significant correlation between GGT elevation and prior alcohol abuse (r=0.259; P=0.039), liver steatosis (r=0.301; P=0.034) and low-density lipoprotein-cholesterol (r=-0.256; P=0.041) was observed. The importance of GGT elevation as an independent predictor of treatment failure was confirmed in a validation cohort (OR2.76; P=0.026). While GGT elevation emerged as an independent predictor of treatment failure in both the derivation and the validation cohort, no independent associations between metabolic factors and treatment failure were observed. Thus, our findings suggest that GGT elevation is an independent predictor of treatment failure in HIV/HCV that can easily be incorporated into predictive algorithms.