Impact of Obefazimod on Viral Persistence, Inflammation, and Immune Activation in People With Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy.

Autor:	Bernal S; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Department of Infectious Diseases and Immunity, School of Medicine, University of Vic-Central University of Catalonia, Vic, Spain., Puertas MC; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain., Morón-López S; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain., Cranston RD; Department of Infectious Diseases, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain., Urrea V; IrsiCaixa AIDS Research Institute, Badalona, Spain., Dalmau J; IrsiCaixa AIDS Research Institute, Badalona, Spain., Salgado M; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.; Germans Trias i Pujol Research Institute, Badalona, Spain., Gálvez C; IrsiCaixa AIDS Research Institute, Badalona, Spain., Erkizia I; IrsiCaixa AIDS Research Institute, Badalona, Spain., McGowan I; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Scherrer D; Abivax, Paris, France., Revollo B; Fundació Lluita contra les Infeccions, Badalona, Spain.; Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain., Sirera G; Fundació Lluita contra les Infeccions, Badalona, Spain.; Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain., Santos JR; Fundació Lluita contra les Infeccions, Badalona, Spain.; Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain., Clotet B; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Department of Infectious Diseases and Immunity, School of Medicine, University of Vic-Central University of Catalonia, Vic, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.; Fundació Lluita contra les Infeccions, Badalona, Spain.; Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain., Paredes R; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Department of Infectious Diseases and Immunity, School of Medicine, University of Vic-Central University of Catalonia, Vic, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.; Fundació Lluita contra les Infeccions, Badalona, Spain.; Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain., Martinez-Picado J; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Department of Infectious Diseases and Immunity, School of Medicine, University of Vic-Central University of Catalonia, Vic, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.; Germans Trias i Pujol Research Institute, Badalona, Spain.; Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Nov 02; Vol. 228 (9), pp. 1280-1291.
DOI:	10.1093/infdis/jiad251
Abstrakt:	Background: Persistence of viral reservoirs has been observed in people with human immunodeficiency virus (HIV), despite long-term antiretroviral therapy (ART), and likely contributes to chronic immune activation and inflammation. Obefazimod is a novel drug that inhibits human immunodeficiency virus type 1 (HIV-1) replication and reduces inflammation. Here we assess whether obefazimod is safe and might impact HIV-1 persistence, chronic immune activation, and inflammation in ART-suppressed people with HIV. Methods: We evaluated obefazimod-related adverse events, changes in cell-associated HIV-1 DNA and RNA, residual viremia, immunophenotype, and inflammation biomarkers in blood and rectal tissue. We compared 24 ART-suppressed people with HIV who received daily doses of 50 mg obefazimod for 12 weeks (n = 13) or 150 mg for 4 weeks (n = 11) and 12 HIV-negative individuals who received 50 mg for 4 weeks. Results: The 50- and 150-mg doses of obefazimod were safe, although the 150-mg dose showed inferior tolerability. The 150-mg dose reduced HIV-1 DNA (P = .008, median fold change = 0.6) and residual viremia in all individuals with detectable viremia at baseline. Furthermore, obefazimod upregulated miR-124 in all participants and reduced the activation markers CD38, HLA-DR, and PD-1 and several inflammation biomarkers. Conclusions: The effect of obefazimod by reducing chronic immune activation and inflammation suggests a potential role for the drug in virus remission strategies involving other compounds that can activate immune cells, such as latency-reversing agents. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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