학술논문
Impact of Obefazimod on Viral Persistence, Inflammation, and Immune Activation in People With Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy.
Document Type
Academic Journal
Author
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.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
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.)
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.)