Therapeutic blockade of IL-1β in PWH reduced the HIV reservoir via mechanisms of enhanced CD8 and CD4 effector function and reversal of monocyte dysfunction
Year: 2026
Type: preprint
Abstract: ABSTRACT Chronic IL-1β-driven inflammation contributes to cardiovascular risk and potentially HIV reservoir persistence in people with HIV (PWH); the effects of direct IL-1β blockade on HIV persistence have not been defined. We show in a cohort of PWH that canakinumab, an anti-IL-1β monoclonal antibody, is associated to the upregulation (Cana_Up) or the downregulation (Cana_Down) of unique sets of genes that are both associated with reduced HIV reservoir. Cana_Up genes are expressed mostly by CD4 and CD8 T cells and mapped to pathways of cell cycling (Myc, E2F, G2M) and Antigen Cross-Presentation. Th17 cells in the blood and gut tissue require IL-1 to differentiate and concomitantly express pathways reduced by canakinumab that lead to reduced reservoir. Participants with reduced reservoir after canakinumab showed significant enhancement of HIV-specific CD4 and CD8 effector function with increased frequencies of cells expressing the effector proteins IFNγ and Granzyme B and the marker of degranulation CD107a. CD14+ monocytes with the highest level of IL-1β also expressed the highest levels of Cana_Down genes that included inflammatory pathways (NF-kB, RELA) and PRC1/2 complex members that regulate epigenetic mediated closure of chromatin (EZH2, JARID2). These findings establish a mechanistic rationale for IL-1β blockade as a therapeutic intervention that effectively target the HIV reservoir by restoring functional HIV specific adaptive immune responses and reversing monocyte driven inflammatory dysfunction.
Source: medRxiv
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213465637