Background:  In the majority of HCV/HIV-co-infected subjects, HCV precedes HIV infection, but cases of acute HCV in HIV⁺ persons demonstrate that the opposite sequence of infection occurs. Since CD4⁺ and CD8⁺ T cells are implicated in the control and pathogenesis of HCV, we asked whether they are primed in HIV⁺ subjects following natural infection and whether they exert immune control. 

Methods:  We performed analyses of virus-specific immune responses for 6 subjects with prior HIV-1 infection and subsequent HCV seroconversion, 4 analyzed 6 to 50 months after seroconversion and 2 analyzed during the acute phase. For acute subjects, samples were collected every 1 to 2 weeks early in infection, prior to seroconversion in 1 case, with a follow-up period of 17 to 35 weeks. No interferon (IFN)-a was given during the study period. IFN-γ responses were mapped by full genome ELISpot using peripheral blood mononuclear cells (PBMC) and tracked over time. Viral loads were determined by Roche Amplicor assay. 

Results:  Of 6 subjects, 5 demonstrated T-cell responses against HCV, including 2 of 2 acutely infected subjects as further detailed. Subject A had a CD4 of 919 cells/mm³, with HIV viral load < 50 on ART. Subject B had a CD4 of 493 cells/mm³, with HIV viral load of 109,000 copies/mL off therapy. Peak HCV RNA levels were 13.0 x 10⁶ and 76.0 x 10⁶ IU/mL, respectively. In the first 3 weeks, a > 3 log drop of HCV viral load was observed in each case, correlating with a multispecific CD4⁺ and CD8⁺ IFN-γ response. Subject A achieved a nadir HCV viral load of 1700 IU/mL, but virus rebounded to ~3.0 x 10⁶ IU/mL, associated with decline of the T-cell response. Subject B achieved viral suppression to < 600 IU/mL, with intermittent rebounds detected subsequently. Interestingly, HIV viral load declined during the early acute phase of HCV from 109,000 to 133 copies/mL. This was not apparently related to GB virus type C (GBV-C) co-infection, down-regulation of CCR5, or dynamics in the HIV-1-specific IFN-γ response. 

Conclusions:   Our data indicate that HIV serostatus alone does not result in primary failure to generate an immune response against HCV. During the acute phase, these responses correlated with initial control of HCV viremia in HIV⁺ individuals. HIV viral load down-regulation was observed in 1 subject during acute HCV, and further studies are examining the potential mechanism for this phenomenon. These data are of relevance to the prospect of immunotherapies versus HCV in this clinically important population and shed insight into interactions of the 2 viruses.

Keywords: Hepatitis C virus; T lymphocytes; Acute infection