Abstract
Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.
Highlights
Interactions of human immunodeficiency virus (HIV) and Antiretroviral Therapy With Neutrophils and PlateletsAbout their impact on neutrophil function, the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment
Infection of individuals with the human immunodeficiency virus (HIV) is characterized by persistent coinfection with opportunistic microbes
This contention is supported by a study reported by Bowers et al, who found that neutrophils in the blood of HIV-infected individuals expressed high levels of programmed death-ligand 1 (PD-L1) that correlated with the expression of programmed death-1 (PD-1) and CD57 on CD4+ and CD8+ T-lymphocytes [22]
Summary
About their impact on neutrophil function, the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD This narrative review is focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions
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