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

Abstract

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 log10 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 log10 cop/ml versus 4.99 log10 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.

The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy

“…These fluctuations in the TTV level strongly suggest that analysis of the salivary TTV level is a sensitive biomarker for CD4+ status and HIV production in HIVpositive individuals currently undergoing ART. Our findings are consistent with earlier studies that demonstrated an association between the extent of TTV viremia in the systemic circulation and immune dysfunction in HIV-positive individuals (12,13,(20)(21)(22). The analysis of TTV titers in bone marrow and spleen tissues also confirmed that elevations in TTV parallel AIDS progression (22).…”

“…Our observation of elevated salivary TTV levels in HIVpositive subjects with AIDS-KS as compared to asymptomatic HIV-positive individuals is also consistent with this association. Investigations of the rate of TTV detection in blood from HIV-positive individuals have varied from <50% to >90% (13,20,21,23). This discordance is likely due in large part to the choice of primers utilized for TTV detection (11,13,24,25).…”

SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis – a cohort study

“…TTV, a highly prevalent and non-pathogenic small nonenveloped DNA virus, is an emerging marker to monitor immunosuppression in recipients of solid organ transplantations ( 17 , 20 ) and in patients with rheumatologic disease ( 21 ). Moreover, TTV is associated with immunocompetence in patients with HIV ( 22 ) and with response to SARS-CoV-2 vaccination in immunocompromised patients ( 18 , 23 ). TTV copy numbers in our sample, independent of type of apheresis, were comparable to those in healthy population, suggesting a less immunocompromised cohort compared to mentioned reference cohorts.…”

Integrated Immunologic Monitoring in Solid Organ Transplantation: The Road Toward Torque Teno Virus-guided Immunosuppression

“… 70 , 71 In patients infected with HIV, TTV load was predictive for the course of immune recovery. 72 Recently, an association has been shown between TTV load and response to severe acute respiratory syndrome coronavirus type 2 vaccination in KTX recipients. 73 According to these findings, the central hypothesis of immune monitoring using TTV in SOT has formed: if the immune system is strong, the TTV load is low; this indicates a risk for organ rejection.…”