Pegylated IFN-α-induced NK cell activation is associated with HIV-1 DNA decline in ART-treated HIV-1/HCV co-infected patients

Abstract

Background

IFN-α can potently reduce HIV-1 replication in tissue culture and animal models, but may also modulate residual viral reservoirs that persist despite suppressive antiretroviral combination therapy. However, mechanisms leading to viral reservoir reduction during IFN-α treatment are unclear.

Methods

We analyzed HIV-1 gag DNA levels in CD4 T cells by digital droplet PCR and CD8 T and NK cell phenotypes by flow cytometry in a cohort of ART-treated HIV-1/HCV co-infected patients (n=67) undergoing treatment for Hepatitis C infection with pegylated IFN-α and Ribavirin for an average of 11 months.

Results

We observed that IFN-α treatment induced a significant decrease in CD4 T cells counts (p<0.0001), in CD4 T cell-associated HIV-1 DNA copies (p=0.002) and in HIV-1 DNA copies per microliter of blood (p<0.0001) in our study patients. Notably, HIV-1 DNA levels were unrelated to HIV-1-specific CD8 T cells responses. In contrast, proportions of total NK cells, of CD56^brightCD16^- NK cells and of CD56^brightCD16⁺ NK cells were significantly correlated with reduced levels of CD4 T cell-associated HIV-1 DNA during IFN-α treatment, especially when co-expressing the activation markers NKG2D and NKp30.

Conclusion

These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.