AI Summary
The research study focuses on the use of anti-IL-10 and anti-PD-1 treatment in controlling SIV viral rebound following analytical treatment interruption in rhesus macaques. The results show that a combination of these treatments led to durable control of viral rebound in most subjects. Key findings included the induction of inflammatory cytokines, proliferation of effector CD8+ T cells, and reduced expression of BCL-2 in CD4+ T cells. Higher levels of memory T cells expressing TCF-1 and SIV-specific CD4+ and CD8+ T cells were associated with lower viral load. This research provides insights into achieving long-lasting control of HIV and/or SIV following ART discontinuation.
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)mac239-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.
Antiretroviral therapy (ART) does not cure human immunodeficiency virus (HIV) infection1. Viral load (VL) generally rebounds on treatment interruption