%0 Journal Article
%A Hua, Stephane
%A Vigano, Selena
%A Tse, Samantha
%A Zhengyu, Ouyang
%A Harrington, Sean
%A Negron, Jordi
%A Garcia-Broncano, Pilar
%A Marchetti, Giulia
%A Genebat, Miguel
%A Leal, Manuel
%A Resino, Salvador
%A Ruiz-Mateos, Ezequiel
%A Lichterfeld, Mathias
%A Yu, Xu G
%T Pegylated Interferon-α-Induced Natural Killer Cell Activation Is Associated With Human Immunodeficiency Virus-1 DNA Decline in Antiretroviral Therapy-Treated HIV-1/Hepatitis C Virus-Coinfected Patients.
%D 2018
%U http://hdl.handle.net/10668/11943
%X BackgroundInterferon 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.MethodsWe 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.ResultsWe 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.ConclusionsThese data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells .
%K Antiretroviral Therapy, Highly Active
%K Coinfection
%K HIV Infections
%K Hepacivirus
%K Lymphocyte Activation
%K Polyethylene Glycols
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