Background:  Therapy of acute hepatitis C virus (HCV) infection results in a sustained virological response in the majority of mono-infected patients. A broad HCV-specific CD4⁺ response correlates with spontaneous resolution of acute HCV infection, but no data exist characterizing the immunologic responses primed during concomitantly acquired acute HCV/HIV co-infection. Here, we present detailed clinical and immunologic analysis of three individuals following concomitant acute HCV/HIV infection.

Methods:  Peripheral blood mononuclear cells (PBMC) and viral loads were preserved longitudinally during the course of the disease in 3 patients. Patients with resolved HCV mono-infection and chronic HIV/HCV co-infection served as controls. HIV-specific responses were assessed by enzyme-linked immunosorbent spot (ELISpot) assay and HCV-specific CD4⁺ responses by standard proliferative assays (CSFE) and by a sensitive ELISpot assay using pre-stimulated expanded autologous T cell lines.

Results:  In the 3 acutely HIV/HCV-co-infected patients, anti-HCV treatment was started with pegylated interferon-alpha (peg-IFN-a) for a mean of 32 weeks and ART was co-administered during primary infection. All patients achieved a HIV viral load <50 copies/mL during ART. After cessation of ART, 2 subjects showed sustained control of HIV replication (viral load <1500 copies/mL), which correlated with proliferative responses against recombinant HIV proteins and strong HIV-specific CD8⁺ cytotoxic T lymphocyte (CTL) responses. These responses were absent in the remaining patient with acute co-infection resulting in uncontrolled viral replication and re-introduction of HAART. All 3 subjects achieved a sustained virological response for HCV after 24 weeks (1 GT1, 2 GT3). No significant HCV-specific proliferative responses were detected but multi-specific HCV CD4 responses to non-structural peptides NS3 and NS4 could be recovered in expanded cell lines from 2 of these patients. These responses were comparable to immunocompetent subjects who resolve HCV mono-infection spontaneously. However, the breadth and magnitude of responses was lower in HIV/HCV co-infection. No HCV-specific CD4 responses were detected in the third patient with acute HIV/HCV co-infection who had the lowest CD4 nadir during primary HIV infection (<200 cells/µL).

Conclusions:  Anti- HIV and HCV therapy should be administered early in the setting of concomitant acute HCV/HIV co-infection, since clearance of HCV is possible even during primary HIV infection. HCV-specific T cell immunity is generated to some extent during primary HIV infection and can be preserved by HCV treatment.