The impact of DAA-mediated HCV eradication on CD4+ and CD8+ T lymphocyte trajectories in HIV/HCV coinfected patients: Data from the ICONA Foundation Cohort

HCV infection has been hypothesized as a contributor of poor CD4(+) recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4(+), CD8(+) cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV-RNA <= 50 copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4(+), CD8(+) and CD4/CD8 changes 12 months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53 years (IQR 50-56). At DAA initiation, CD4(+) T cell count was <350 cells/mm(3) in 164 patients (17.5%), and 246 patients (26.2%) had liver stiffness>12.5 kPa. Trends of CD4(+) and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4(+) change +17.6 cells/mm(3) (95%CI -33.5; 69.4, p = 0.494); CD4/CD8 change 0.013 (95%CI -0.061; 0.036, p = 0.611). However, patients treated with ribavirin (RBV)-free DAA showed a significant decrease in CD8(+) cells (-204.3 cells/mm(3), 95%CI -375.0;-33.4, p = 0.019), while patients treated with RBV experienced CD8(+) cell increase (+141.2 cells/mm(3), 95%CI 40.3; 242.1, p = 0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4(+) T cell recovery in PLWHIV. However, a fast decline of CD8(+)T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.