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/mm3 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/mm3 (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/mm3 , 95%CI -375.0;-33.4, p=0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3 , 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 favorable effect of HCV clearance on the general state of immune activation.