Vol.:(0123456789) 1 3 Medical Microbiology and Immunology https://doi.org/10.1007/s00430-019-00619-4 ORIGINAL INVESTIGATION Infuence of Hepatitis C virus coinfection on immune reconstitution in HIV subjects María Noel Badano 1  · Cecilia Parodi 1  · Natalia Aloisi 1  · Marcelo Corti 2  · María Marta Elizalde de Bracco 1  · Patricia Baré 1 Received: 13 September 2018 / Accepted: 13 May 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Despite successful HIV suppression by antiretroviral treatment (ART), immune activation may persist in HIV patients, contributing to an impaired immunological reconstitution and disease progression. Information regarding Hepatitis C virus (HCV) coinfection as a factor that accounts for immune activation in HIV subjects remains unclear. Furthermore, most studies have been carried out considering HIV/HCV patients as a whole, without taking into account the presence or absence of liver damage. Therefore, it is unknown if HCV and/or its liver-related disease could act as two independent factors contributing to the immune activation. In this study, we investigated the presence of immune activation in a cohort of 50 HIV/HCV patients by measuring cytokine levels, CD4 + T-cell counts and CD4/CD8 ratios. Six patient groups were defned according to HIV viral load, HCV status, and liver disease to assess the impact of each of these factors on immune activation and reconstitution in HIV/HCV patients. Only subjects with controlled HIV infection and cleared HCV displayed immunological parameters within normal ranges. The mere presence of HCV contributes to immune activation leading to an inappropriate immuno- logical reconstitution. This state exacerbates in the presence of HCV-associated liver disease. Our results suggest that ART is not enough to suppress immune activation in the context of HIV/HCV coinfection, since both HCV and its liver-related disease would contribute to the immune activation. Given that immune activation worsens immunological reconstitution and clinical status, these results support the priority of HCV treatment in HIV/HCV patients and suggest the monitoring of their liver status. Keywords HIV/HCV coinfection · Antiretroviral treatment · Immune activation · Liver disease · Immunological reconstitution Introduction Generalized immune activation is one of the hallmarks of HIV infection. Basically, every component of the immune system is in a hyperactive state during chronic untreated HIV infection. Non-specifc T-cell activation and proliferation, increased T-cell turnover, polyclonal B-cell activation, and elevated plasma levels of proinfammatory cytokines are characteristics of this phase. Most important, T-cell acti- vation is associated with CD4 + T-cell depletion, sustained viral replication, and HIV disease progression. Diferent mechanisms are thought to contribute to the generalized immune system activation including persistent HIV repli- cation, bacterial translocation associated with the loss of gut barrier integrity, and the presence of other coinfections [1–4]. Antiretroviral treatment (ART) hits directly on HIV replication, thus removing one of the main sources of stimuli for immune activation. In general, suppression of plasma HIV viral load by ART is followed by immunological recon- stitution usually noted as an increase in the circulating CD4 + T-cell counts [5]. However, even after several years of sus- tained plasma HIV viral load suppression, some patients show an insufcient CD4 + T-cell count recovery, reaching Edited by: Christian Bogdan. * María Noel Badano noebadano@yahoo.com.ar 1 Laboratory of Immunology, Instituto de Medicina Experimental (IMEX)-Consejo Nacional de Investigaciones Científcas y Técnicas (CONICET), Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, CABA 1425, Buenos Aires, Argentina 2 Fundación de la Hemoflia, Soler 3483, CABA 1174, Buenos Aires, Argentina