HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria

Abstract

HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response.

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

“…Furthermore, early HAART initiation enables the preservation of functional gut follicular helper CD4+ T cells and Env-specific memory B cells, which facilitates the development of functionally relevant HIV-1 antibodies [140][141][142]. Most recently, Planchais et al investigated the impact of HAART initiation timing on the intestinal B-cell antibody repertoire from colon tissues of individuals treated either during the acute (eART) or chronic (lART) phases of infection [143]. They demonstrated that HIV-1 HAART treatment timing shapes the systemic and gut mucosal memory B-cell repertoire.…”