Background: GB Virus C (GBV-C) has been shown to be associated with improved survival in HIV-1-infected individuals. However, the exact mechanism for slower disease progression in HIV-1/GBV-C co-infection remains to be identified. As cellular immune responses play a critical role in the control of viral replication, understanding the impact of co-infection with GBV-C on T cell responses directed against HIV-1 may yield important insights for understanding disease progression and immune control. Furthermore to date no data are available on cellular immune responses directed against GBV-C.

Methods:  We screened a cohort of 100 HIV-1-infected patients at different stages of HIV-1 infection for the presence of GBV-C-RNA using nested RT-PCR. A subset of this cohort was evaluated for T cell responses directed against the entire expressed HIV-1 genome using an IFN-g Elispot assay. Total breadth and magnitude of the HIV-1-specific T cell response were compared in individuals with and without GBV-C co-infection. Selected study subjects were also screened for GBV-C-specific T cell responses directed against the NS3 protein using overlapping peptides based on the patients’ autologous GBV-C sequences in IFN-g ELISpot and intracellular cytokine staining (ICS) assays.

Results: GBV-C RNA was detected in 49% of the study subjects. HIV-1 plasma viral loads were significantly lower in GBV-C-RNA positive compared to GBV-C-RNA negative individuals (p <0.02). HIV-1 specific CD8 T-cell responses were detectable in all subjects and no significant difference in the number of epitopes targeted and the magnitude of the total HIV-1-specific response was observed between the 2 groups. In a subset of GBV-C positive individuals examined in detail, we detected GBV-C-specific CD4 and CD8 T-cell responses by ELISpot and ICS assays, which were narrowly directed and of low magnitude ex vivo.

Conclusions:  From these studies we conclude that GBV-C co-infection is frequently seen in HIV-1-infected individuals and that it is associated with lower HIV-1 viral loads in co-infected patients. Our data further suggest that co-infection with GBV-C does not influence the breadth and the magnitude of the HIV-1-specific CD8 response. This study also provides the first evidence of detectable GBV-C-specific T cell responses, which need to be investigated further. The exact mechanisms of a more favorable prognosis for disease progression in GBV-C/HIV-1 co-infected individuals remain to be identified.

Keywords: HIV; GBV-C; Cellular immune responses