HIV long term nonprogressors have increased immune responsiveness to other viral pathogens

Some HIV-infected persons are able to maintain a relatively normal immune state for extended periods, in some cases more than a decade, without taking highly active antiretroviral therapy.

In some studies, these long-term nonprogressors (LTNP) have been found to have vigorous CD8+ T cell responses to HIV, but it is not clear from these data whether this immune responsiveness is specific to HIV or is reflective of a generalized heightened immune response. In order to evaluate the specificity of heightened CD8+ T cell responses in LTNP, investigators at Case Western Reserve University examined CD8+ T cell responses to hepatitis C virus (HCV) in HCV-HIV coinfected and HCV mono-infected individuals.

The cross-sectional study, published in AIDS, involved a total of 76 patients. Forty-two of the patients were HCV monoinfected, 32 with and 10 without chronic HCV infection. Patients without chronic HCV infection had no detectable HCV RNA and had persistently normal alanine aminotransferase (ALT) over one year. Seventeen HCV-HIV coinfected patients were enrolled, 11 who were considered HCV-HIV progressors and six who were considered LTNP.

These patients had both HIV and HCV antibodies and either HCV serum RNA or recombinant immunoblot assay (RIBA) reactivity. Patients considered to be HCV-HIV LTNP had no clinical manifestations of HIV infection for at least seven years and had CD4+ T cell counts >400 cells/mm3 without HIV therapy. Seven HIV monoinfected patients were enrolled, and had HIV antibody, a detectable HIV viral load, and no detectable HCV antibody. None of the enrolled patients had previously received HCV therapy. Finally, 10 healthy controls were enrolled, all of whom had no HCV or HIV antibodies.

The investigators found that five of six HCV-HIV LTNP had HCV-specific CD8+ T cell responses. In contrast, such responses were observed in only two of the 32 HCV monoinfected patients with and two of the 10 HCV monoinfected patients without chronic infection. None of the 11 HCV-HIV progressors were found to have these immune responses. In addition, the frequency of HCV-specific CD8+ T cells and number of HCV peptides recognized were significantly higher in the HCV-HIV LTNP than in other groups.

The authors conclude, “Our data indicate that HCV-specific IFN-?-producing CD8 memory cell frequency is preserved in HCV-HIV coinfected LTNP, while this is not the case for most HCV-HIV progressors and HCV singly infected individuals.

“Additionally, HCV-HIV coinfected LTNP maintained more CD8 HCV-specific IFN-?-producing cells, and targeted more HCV peptides, than did persons in other groups. These results indicate that the HIV LTNP phenotype also affects the HCV-specific CD8 memory effector pool frequency in coinfected individuals.”