Cellular responses against hepatitis C virus (HCV) are impaired in HIV/HCV-coinfected patients showing uncontrolled viral replication and immune suppression. Very few studies have explored to what extent HCV-specific response improves as a consequence of control of HIV replication by highly active antiretroviral therapy. We compared HCV-specific T-cell responses between HIV/HCV-coinfected patients, showing complete viral suppression, and HCV-monoinfected patients.
HCV-specific T-cell responses were examined in 50 interferon-naive patients with chronic hepatitis C: 27 HCV-monoinfected and 23 HIV/HCV-coinfected on highly active antiretroviral therapy and undetectable HIV load. Production of interferon-γ and tumor necrosis factor-α was simultaneously measured in response to genotype-matched overlapping peptides spanning the whole HCV proteome by flow cytometry. Differences between groups were tested using nonparametric tests.
More than half of patients presented CD4+ (60%) or CD8+ (57%) response to at least one HCV protein with no significant differences between both groups. Intensity and breadth of response were also similar between groups. The functional profile of response was represented, in both groups, mainly by monofunctional subsets, although there were some differences between CD4+ and CD8+ T-cell response. CD8+ response was mediated almost exclusively by monofunctional interferon-γ+ cells, whereas bifunctional interferon-γ+tumor necrosis factor-α+ cells showed a moderate contribution to CD4+ response. Most of the CD8+ response was mediated by interferon-γ, whereas tumor necrosis factor-α was the highest contributor to CD4+ response.
Our study demonstrates that in HIV/HCV-coinfected patients with maximal HIV suppression under highly active antiretroviral therapy, several characteristics of anti-HCV T-cell response are similar to those found in HCV-monoinfected patients, suggesting that control of HIV replication might improve HCV-specific T-cell response in HIV/HCV-coinfected patients.
From the *Department of Infectious Diseases and the †Hepatology Unit-CIBEREHD, Hospital Carlos III, Madrid, Spain.
Received for publication October 22, 2010; accepted January 12, 2010.
This work was supported in part by grants from FIPSE (grant number 36617/06), Fundación Investigacion y Educacion en SIDA (IES), Red de Investigacion en SIDA (RIS, FIS-RD06/0006), CIBEREHD, and Agencia Lain Entralgo and the European Union 6th Framework Programme (NEAT, LSHP-CT-2006- 037570).
The authors have no conflicts of interest to disclose.
Correspondence to: José M. Benito, MD, PhD, Infectious Diseases Department, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain (e-mail: firstname.lastname@example.org).