Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.
Susan Pereira RibeiroZachary StronginHugo SoudeynsFelipe Ten-CatenKhader GhneimGabriela Pacheco SanchezGiuliana Xavier de MedeirosPerla Mariana Del Río-EstradaAdam-Nicolas PelletierTimothy HoangKevin NguyenJustin HarperSherrie JeanChelsea WallaceRobert BalderasJeffrey D LifsonGopalan RaghunathanEric RimmerCinthia PastuskovaGuoxin WuLuca MicciRuy M RibeiroChi Ngai ChanJacob D EstesGuido SilvestriDaniel M GormanBonnie J HowellDaria J HazudaMirko PaiardiniRafick-Pierre SekalyPublished in: Nature immunology (2024)
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac 239 -infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8 + T cells in lymph nodes and reduced expression of BCL-2 in CD4 + T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4 + and CD8 + T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.
Keyphrases
- antiretroviral therapy
- human immunodeficiency virus
- hiv infected
- hiv positive
- hiv aids
- hiv infected patients
- lymph node
- sars cov
- hepatitis c virus
- poor prognosis
- gestational age
- newly diagnosed
- regulatory t cells
- early stage
- immune response
- dendritic cells
- hiv testing
- combination therapy
- preterm birth
- high density
- rectal cancer