Residual viremia is linked to a specific immune activation profile in HIV-1-infected adults under efficient antiretroviral therapy

Mehwish Younas (1, 2) , Christina Psomas (1, 3, 2) , Christelle Reynes (4, 2) , Renaud Cezar (5) , Lucy Kundura (1, 2) , Pierre Portalès (2) , Corinne Merle (3, 2) , Nadine Atoui (3, 2) , Céline Fernandez (3, 2, 6) , Vincent Le Moing (3, 6) , Claudine Barbuat (5) , Albert Sotto (5, 7) , Robert Sabatier (4, 2) , Audrey Winter (1, 2) , Pascale Fabbro (5, 8) , Thierry Vincent (2, 9) , Jacques Reynes (3, 2, 6) , Pierre Corbeau (1, 2, 5)

1 IGH - Institut de génétique humaine
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France
4 IGF - Institut de Génomique Fonctionnelle
5 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
6 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
7 VBMI - Virulence bactérienne et maladies infectieuses
8 IDESP - Institut Desbrest de santé publique
9 INM-RAS - Institute of Numerical Mathematics [Moscou]

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.

Mots clés: Blip; Coagulation; Endothelium activation; Inflammation; Low-level viremia; Virologic responder

Domaines: Sciences du Vivant [q-bio]; Immunologie

Mehwish Younas, Christina Psomas, Christelle Reynes, Renaud Cezar, Lucy Kundura, et al.. Residual viremia is linked to a specific immune activation profile in HIV-1-infected adults under efficient antiretroviral therapy. Frontiers in Immunology, 2021, 12, pp.663843. ⟨10.3389/fimmu.2021.663843⟩. ⟨hal-03205174⟩