Background: Interferon alpha (IFN-α) can potently reduce human immunodeficiency virus type 1 (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 polymerase chain reaction and CD8 T-cell and natural killer (NK) cell phenotypes by flow cytometry in a cohort of antiretroviral therapy-treated HIV-1/hepatitis C virus-coinfected 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-cell counts (P < .0001), in CD4 T-cell-associated HIV-1 DNA copies (P = .002) and in HIV-1 DNA copies per microliter of blood (P < .0001) in our study patients. Notably, HIV-1 DNA levels were unrelated to HIV-1-specific CD8 T-cell responses. In contrast, proportions of total NK cells, CD56brightCD16- NK cells, and CD56brightCD16+ NK cells were significantly correlated with reduced levels of CD4 T-cell-associated HIV-1 DNA during IFN-α treatment, especially when coexpressing the activation markers NKG2D and NKp30. Conclusions: These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.
Pegylated IFN-α-induced NK cell activation is associated with HIV-1 DNA decline in ART-treated HIV-1/HCV co-infected patients / S. Hua, S. Vigano, S. Tse, O. Zhengyu, S. Harrington, J. Negron, P. Garcia-Broncano, G. Marchetti, M. Genebat, M. Leal, S. Resino, E. Ruiz-Mateos, M. Lichterfeld, X.G. Yu. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1058-4838. - 66:12(2018 Jun 01), pp. 1910-1917.
|Titolo:||Pegylated IFN-α-induced NK cell activation is associated with HIV-1 DNA decline in ART-treated HIV-1/HCV co-infected patients|
|Parole Chiave:||HIV-1 reservoir; IFN-α; NK cells|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
|Data di pubblicazione:||1-giu-2018|
|Data ahead of print / Data di stampa:||20-dic-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/cid/cix1111|
|Appare nelle tipologie:||01 - Articolo su periodico|