Cardiovascular Disease and Thrombosis in HIV Infection

Perkins, Megan; Joseph, Sarah; Dittmer, Dirk P.; Mackman, Nigel

doi:10.1161/atvbaha.122.318232

Cited by 33 publications

(46 citation statements)

References 242 publications

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“…It is important to note that the HIV viral proteins themselves also have significant cardiovascular effects. The viral proteins Tat, Nef, and Env have been shown to be key factors in chronic inflammation that ultimately leads to endothelial cell dysfunction and atherosclerosis ( Perkins et al, 2023 ). Tat, in particular, is a multifunctional protein that can lead to the activation of transcription factors including NFkB (nuclear factor kB), TNFα/β, IL-2, and IL-6 ( Hofman et al, 1993 ; Buonaguro et al, 1994 ; Perkins et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…The viral proteins Tat, Nef, and Env have been shown to be key factors in chronic inflammation that ultimately leads to endothelial cell dysfunction and atherosclerosis ( Perkins et al, 2023 ). Tat, in particular, is a multifunctional protein that can lead to the activation of transcription factors including NFkB (nuclear factor kB), TNFα/β, IL-2, and IL-6 ( Hofman et al, 1993 ; Buonaguro et al, 1994 ; Perkins et al, 2023 ). This protein can also act like CC chemokines and interact with CCR2/3 to recruit monocytes that contribute to chronic inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…This protein can also act like CC chemokines and interact with CCR2/3 to recruit monocytes that contribute to chronic inflammation. In addition, Tat will act at the level of endothelial cells by inducing expression of adhesion receptors ICAM-1, VCAM-1 and E-selectins ( Hofman et al, 1993 ; Perkins et al, 2023 ). These actions caused by Tat raise concerns for the development of cardiovascular sequelae in patients living with HIV.…”

Section: Introductionmentioning

confidence: 99%

“…Another important protein to consider is Nef, a small accessory protein of HIV. This protein downregulates Major Histocompatibility Complex class I/II (MHC I/II) as well as CD80 and CD86 ( Perkins et al, 2023 ). Nef protein will cause apoptosis in bystander T cells regardless of uninfected/infected state ( Lenassi et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the Env protein which in normal functioning of the HIV virus acts as the viral envelope protein. This HIV protein has been shown to induce expression ICAM-1, apoptosis of endothelial cells, and reduction of eNOS ( Ullrich et al, 2000 ; Huang et al, 2001 ; Ren et al, 2002 ; Perkins et al, 2023 ). Additionally, Env proteins have been implicated in T-cell activation-dependent apoptosis and lead to antibody dependent cellular cytotoxic mediated killing of uninfected cells expressing CD4 ( Banda et al, 1992 ; Forthal and Finzi, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV

Batta

King²,

Cooper³

et al. 2023

Front. Physiol.

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With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s–601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245–50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV

Batta

King²,

Cooper³

et al. 2023

Front. Physiol.

View full text Add to dashboard Cite

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Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease

Lembas,

Załęski,

Peller

et al. 2023

Cardiovasc Toxicol

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The developments in HIV treatments have increased the life expectancy of people living with HIV (PLWH), a situation that makes cardiovascular disease (CVD) in that population as relevant as ever. PLWH are at increased risk of CVD, and our understanding of the underlying mechanisms is continually increasing. HIV infection is associated with elevated levels of multiple proinflammatory molecules, including IL-6, IL-1β, VCAM-1, ICAM-1, TNF-α, TGF-β, osteopontin, sCD14, hs-CRP, and D-dimer. Other currently examined mechanisms include CD4 + lymphocyte depletion, increased intestinal permeability, microbial translocation, and altered cholesterol metabolism. Antiretroviral therapy (ART) leads to decreases in the concentrations of the majority of proinflammatory molecules, although most remain higher than in the general population. Moreover, adverse effects of ART also play an important role in increased CVD risk, especially in the era of rapid advancement of new therapeutical options. Nevertheless, it is currently believed that HIV plays a more significant role in the development of metabolic syndromes than treatment-associated factors. PLWH being more prone to develop CVD is also due to the higher prevalence of smoking and chronic coinfections with viruses such as HCV and HBV. For these reasons, it is crucial to consider HIV a possible causal factor in CVD occurrence, especially among young patients or individuals without common CVD risk factors.

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