Human Immunodeficiency Virus and Cardiovascular Disease: Revisiting the Inflammation–Thrombosis Axis

Introduction

There are more than 37 million people living with the human immunodeficiency virus (PLWH) worldwide with an estimated 2 million new infections occurring annually. Antiretroviral medication has dramatically prolonged the life expectancy of PLWH resulting in a growing population of older PLWH. Based on recent data from the Netherlands, by 2030, 73% of human immunodeficiency virus (HIV)-positive patients will be older than 50 years of age.[1] Despite this increasing life expectancy, there is a twofold increased risk of atherosclerotic cardiovascular disease (ASCVD) and a two- to 10-fold increased risk of venous thromboembolism (VTE). The reasons for the increased risk of cardiovascular disease among PLWH are complex and multifactorial. In addition to a high frequency of traditional risk factors in PLWH, persistent inflammation and coagulopathy appear to contribute to the increased risk of ASCVD and VTE.

HIV-1 infects CD4+ cells, mainly T helper cells, but also macrophages and dendritic cells, and directly or indirectly destroys these cells leading to immune dysfunction and deficiency.[2] HIV is able to activate pattern recognition receptors (PRRs) that promote inflammasome activation in circulating monocyte-derived dendritic cells, human monocytes, and monocyte-derived macrophages.[3] Although combined antiretroviral therapy (cART) suppresses circulating viral counts, there is no complete elimination of viral latency, chronic inflammation, or immune activation. This chronic inflammation in PLWH, despite cART with viral suppression, is probably related to increased traditional risk factors and proinflammatory lipids, certain antiretroviral combinations, low levels of viral replication, coinfection with other pathogens such as cytomegalovirus, and microbial translocation ([Fig. 1]).[4]

Fig. 1 Bidirectional relationship between inflammation and thrombosis in HIV-infected patients. CRP, C-reactive protein; IL-1β, interleukin-1β; IL-6, interleukin 6; sCD163, soluble CD163; TNF-α, tumor necrosis factor-α; vWF, von Willebrand factor.

Contributing to the proinflammatory phenotype in PLWH is lipodystrophy and adipocyte tissue dysfunction.[5] Lipodystrophy (abnormal fat redistribution) is associated with metabolic derangements, such as dyslipidemia and insulin resistance, and is well described following cART initiation.[5] [6] It is not clear whether a particular antiretroviral therapy drug or class of drugs is responsible for the abnormal fat accumulation since lipodystrophy appears to occur to some degree with any combination, even in patients with no prior exposure to protease inhibitors.[7] [8] Adipocyte tissue dysfunction, which is caused by both the HIV infection and certain antiretroviral agents, promotes systemic inflammation through secretion of adipokines.[9] In addition, due to chronic viral load suppression with effective cART among PLWH, there is an increasing frequency of obesity, which promotes insulin resistance and chronic inflammation through adipocyte dysfunction and lipotoxicity.[10]

Publikationsverlauf

Eingereicht: 03. August 2021

Angenommen: 08. September 2021

Artikel online veröffentlicht:
24. Oktober 2021

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