Background:  The role of T cell immunity in chronic hepatitis C virus (HCV) infection and its relationship to HCV replication remains controversial. As in HIV infection, virus replication could be both cause or effect of T cell immunity. We examined the effect of HIV co-infection and of therapy-controlled HCV replication, on HCV-specific CD4⁺ and CD8⁺ T cell responses in patients with chronic HCV.

Methods:  We included 36 patients with chronic HCV who initiated therapy with pegylated interferon (peg-INF) + ribavirin (RBV), and presented early virological response; 17 were co-infected with HIV and 19 were HCV-mono-infected; 82% of co-infected patients were on ART. CD4⁺ and CD8⁺ HCV-specific immune responses were assessed at different time-points following initiation of anti-HCV therapy using intracellular IFN-g staining in response to a panel of overlapping peptides comprising 4 HCV proteins (E2, NS3, NS5a, NS5b). The proportion of patients presenting a positive response (³0.1% of CD4⁺ or CD8⁺ T cells) against the different proteins was compared at each time-point, using the Fisher’s exact test.

Results:  Baseline and month-3 plasma HCV RNA was similar in co-infected and mono-infected patients (5.8+1.1 vs 5.7+0.9 and 3.0+0.7 vs 2.7+0.2, respectively). At baseline, the proportion of patients with positive CD4⁺ and CD8⁺ responses was significantly lower in co-infected than in mono-infected subjects for all HCV proteins (CD4⁺:  7% vs 50%, 0% vs 60%, 0% vs 43%, 13% vs 39%; CD8⁺:  21% vs 38%, 8% vs 44%, 17% vs 43%, 13% vs 50%, for E2, NS3, NS5a and NS5b, respectively). At month 3, CD8⁺ responses against all proteins significantly decreased in HCV-mono-infected patients, and this was maintained over the whole follow-up period. Although the same occurred in the co-infected group, the difference was not significant because of the low proportion of responders at baseline. At month 12, CD8⁺ responses against the 4 HCV proteins were absent in all patients. CD4⁺ responses against NS3 and NS5a significantly diminished in the mono-infected group, whereas responses to E2 and NS5a did not change. In co-infected patients, CD4⁺ responses were already very low at baseline and did not experience any significant variation.

Conclusions:  The existence of HCV-specific T cell immune responses is dependent of continuous antigenic stimulation. They are lower in HIV-co-infected patients and vanish following complete suppression of HCV replication under successful therapy.