Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients

Purpose To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. Methods TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4 + cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4 + cell count and to the extent of CD4 + T-cell increase within the first year of cART. Results TTV DNA was detectable in 96% of the patients’ plasma samples with a median TTV plasma concentration of 5.37 log 10 cop/ml. The baseline CD4 + cell count was negatively correlated with TTV plasma concentration ( p = 0.003). In patients with a CD4 + cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4 + cell recovery of > 200 CD4 + cells/µl (5.68 log 10 cop/ml versus 4.99 log 10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4 + cell count were significantly correlated to CD4 + cell recovery ( p = 0.004). For all other parameters considered, no significant correlation for CD4 + cell recovery was found. Conclusion Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4 + cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4 + cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.