Background:  There is evidence that HIV and hepatitis C virus (HCV) virus interactions may accelerate progression to AIDS and HCV-associated end-stage liver disease. Furthermore, the response to HCV therapy is apparently less satisfactory in HIV/HCV-co-infected individuals, urging the identification of predictive treatment outcome markers to guide therapeutic strategies optimisation. We assessed CD4 homeostasis regulation in HIV/HCV interactions, and the association with early virological response  to anti-HCV therapy.

Methods:  We analyzed 26 HCV-infected patients (15 HIV-co-infected on stable HAART) initiating pegylated interferon alpha-2a (pegIFNa-2a (180 µg/kg) plus ribavirin (1000 to 1200 mg according to weight). CD4, CD8 phenotype, activation, interleukin (IL) -7Ra expression, T cell receptor excision cells (TREC), and plasma IL-7 were measured at baseline and assessed according to early virological response (HCV RNA<15 IU/mL at month 3).

Results:  HCV genotype and HCV RNA were comparable between HIV/HCV-co-infected and HCV-mono-infected patients; at baseline, in co-infected patients median CD4 and HIV RNA were 460 cells/µL and <60 copies/mL, respectively. As compared to HCV-mono-infected, HIV/HCV-co-infected individuals displayed augmented activated/proliferating CD38⁺Ki67⁺CD4 and CD8 (p = 0.05 for CD8⁺CD38; p = 0.04 for Ki67⁺CD4). On the contrary, co-infected patients presented lowest plasma IL-7 (p = 0.02) and TREC⁺CD4 and CD8 (p = 0.05), with a trend toward reduced IL-7Ra⁺CD4 (p = 0.07). Early virological response was obtained in 5 of 11 HCV/HIV-co-infected patients completing 3 months’ anti-HCV therapy (responders); responders and non-responders were comparable in terms of age, HCV genotype, median nadir and baseline CD4, baseline HIV RNA, length of HAART. HIV/HCV non-responders were featured by more elevated baseline proportions of activated CD38⁺CD4 and CD8 (p = 0.05 for CD8⁺CD38), and reduced IL-7Ra⁺CD4 and CD8 (p = 0.01), but comparable TREC and plasma IL-7 (p = 0.2 and p = 0.16, respectively).

Conclusions:  Despite complete HIV RNA suppression and similar viral parameters for HCV in mono- and co-infected patients, HIV/HCV-co-infected patients fail to contain generalised T cell immune hyperactivation and sustain IL-7 dependant de novo CD4 repopulation. We may speculate that increased T cell activation, and reduced IL-7Ra expression are early biomarkers of HCV treatment outcome in HIV/HCV-co-infected patients. Their experimental exploitation may contribute to the design of novel immunotherapeutic approaches.