Inflammatory neutrophil responses and T cell activation in ART-treated SIVmac239-infected rhesus macaques

Modern antiretroviral therapy (ART) regimens have revolutionized the management of human immunodeficiency virus (HIV) and transformed it from a life-threatening disease to a manageable chronic condition. Despite the durable viral suppression associated with ART adherence, people with HIV (PWH) continue to experience chronic immune activation and inflammation, which has been linked with increased risk of developing non-acquired immunodeficiency syndrome (AIDS) comorbidities, including cardiovascular disease, liver disease, or neurocognitive disorders. Importantly, the mechanisms underlying establishment and maintenance of immune activation in ART-treated PWH remain incompletely defined. Here, we used a nonhuman primate model to evaluate associations between markers of systemic immune activation and peripheral neutrophils in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs), both before and after ART. As expected, peripheral frequencies of activated CD4+ and CD8+ T cells were elevated during acute SIV infection and returned to baseline levels following ART initiation. Neutrophil dynamics were impacted during acute SIV infection, including decreased peripheral neutrophil frequencies, increased neutrophil degranulation, and the potential for increased neutrophil extracellular trap (NET) formation. Treatment with ART mitigated these inflammatory neutrophil effector functions. Finally, frequencies of HLA-DR+ CD4+ and CD8+ T cells were significantly positively correlated with frequencies of inflammatory CD62Ldim neutrophils and plasma levels of myeloperoxidase, a component of neutrophil granules. Taken together, these data indicate that neutrophil activity and systemic T cell activation are correlated during acute SIV and early ART. Our work provides insight into associations between neutrophil dynamics and immune activation during HIV/SIV in the context of ART.