Residual Viremia Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults Under Efficient Antiretroviral Therapy

Mehwish Younas,Christelle Reynes,Renaud Cezar,Albert Sotto,Pascale Fabbro,Christina Psomas,Corinne Merle,Vincent Le Moing,Nadine Atoui,Pierre Corbeau,Lucy Kundura,Claudine Barbuat,Robert Sabatier,Pierre Portalès,Jacques Reynes,Céline Fernandez,Thierry Vincent,Audrey Winter

doi:10.3389/fimmu.2021.663843

Abstract

Chronic immune activation persists in persons living with HIV-1 even though they are aviremic under antiretroviral therapy, and fuels comorbidities. In previous studies, we have revealed that virologic responders present distinct profiles of immune activation, and that one of these profiles is related to microbial translocation. In the present work, we tested in 140 HIV-1-infected adults under efficient treatment for a mean duration of eight years whether low-level viremia might be another cause of immune activation. We observed that the frequency of viremia between 1 and 20 HIV-1 RNA copies/mL (39.5 ± 24.7% versus 21.1 ± 22.5%, p = 0.033) and transient viremia above 20 HIV-1 RNA copies/mL (15.1 ± 16.9% versus 3.3 ± 7.2%, p = 0.005) over the 2 last years was higher in patients with one profile of immune activation, Profile E, than in the other patients. Profile E, which is different from the profile related to microbial translocation with frequent CD38+ CD8+ T cells, is characterized by a high level of CD4+ T cell (cell surface expression of CD38), monocyte (plasma concentration of soluble CD14), and endothelium (plasma concentration of soluble Endothelial Protein C Receptor) activation, whereas the other profiles presented low CD4:CD8 ratio, elevated proportions of central memory CD8+ T cells or HLA-DR+ CD4+ T cells, respectively. Our data reinforce the hypothesis that various etiological factors shape the form of the immune activation in virologic responders, resulting in specific profiles. Given the type of immune activation of Profile E, a potential causal link between low-level viremia and atherosclerosis should be investigated.

Highlights

Immune activation (IA)-related comorbidities are becoming a major concern in aviremic HIV-infected persons under antiretroviral therapy (ART) [1]
It is logical to assume that residual viremia should fuel immune activation in virological responders
Some authors have found a link between low-level viremia and IA [12, 13], others have not [14,15,16,17]. This discrepancy might be due to differences in the size and/or bioclinical characteristics of the populations under study, as well as the actual definition of residual viremia

Summary

Introduction

Immune activation (IA)-related comorbidities are becoming a major concern in aviremic HIV-infected persons under antiretroviral therapy (ART) [1]. Many HIV components may directly activate the innate immune system. Gp120 [6] Nef and Vpr [7] have been reported to directly activate monocytes and macrophages, and gp T cells [8]. It has been reported that HIV RNA induces interferon-a production by plasmacytoid dendritic cells via TLR-7 and TLR-9. Even a truncated CD4+ T cell infection may induce caspase-1 activation and IL-1b production in CD4+ T cells [9]. Nef protein is known to interact with the adenosinetriphosphate-binding cassette A1 transporter. This interaction interferes with cholesterol metabolism, and may promote proinflammatory metabolic disorders [11]. Likewise, HIVmediated IA might promote immune senescence, which is an additional cause of IA

Methods

Results

Conclusion