Hua, StephaneVigano, SelenaTse, SamanthaZhengyu, OuyangHarrington, SeanNegron, JordiGarcia-Broncano, PilarMarchetti, GiuliaGenebat, MiguelLeal, ManuelResino, SalvadorRuiz-Mateos, EzequielLichterfeld, MathiasYu, Xu G2023-01-252023-01-252018-06-15Hua S, Vigano S, Tse S, Zhengyu O, Harrington S, Negron J, et al. 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. Clin Infect Dis. 2018 Jun 1;66(12):1910-1917.http://hdl.handle.net/10668/11943BackgroundInterferon 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 .enAntiretroviral Therapy, Highly ActiveCoinfectionHIV InfectionsHepacivirusLymphocyte ActivationPolyethylene GlycolsAdultAgedCohort StudiesDNA, ViralDisease ReservoirsFemaleHIV-1Hepatitis CHumansInterferon-alphaKiller Cells, NaturalMaleMiddle AgedRecombinant ProteinsRibavirinSpainViral Loadresearch article29272392Restricted AccessVIH-1Linfocitos TCélulas asesinas naturalesHepatitis CHepacivirusAntiviralesRibavirinaInfecciones10.1093/cid/cix11111537-6591PMC5982807https://academic.oup.com/cid/article-pdf/66/12/1910/25084671/cix1111.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982807/pdf