Hiv/Aids And Stroke: Is There A Link?

HIV infection can cause stroke through several mechanisms, including opportunistic infection, vasculopathy, cardioembolism, and coagulopathy. The occurrence of stroke and HIV infection might often be coincidental. HIV-associated vasculopathy describes various cerebrovascular changes, including stenosis and aneurysm formation, vasculitis, and accelerated atherosclerosis, and might be caused directly or indirectly by HIV infection, although the mechanisms are controversial. HIV and associated infections contribute to chronic inflammation. Combination antiretroviral therapies (cART) are clearly beneficial, but can be atherogenic and could increase stroke risk. cART can prolong life, increasing the size of the ageing population at risk of stroke.

HIV-associated vasculopathy

Aneurysmal arterial changes

Aneurysmal arterial changes refer to the dilation of blood vessels, which can be intracranial or extracranial. Intracranial aneurysms typically involve the branches of the circle of Willis and can lead to ischaemic or haemorrhagic stroke. Extracranial aneurysms can involve the carotid, aorta, iliac, and other large arteries.

Vasculitis

Vasculitis refers to inflammation of the blood vessel wall. HIV-associated vasculitis is characterised by inflammatory cells in the blood vessel wall, along with associated wall damage. However, the role of HIV in the development of vasculitis is uncertain, as some studies suggest that other infections, such as varicella zoster virus, may be responsible.

Accelerated atherosclerosis

HIV infection and its treatment with combination antiretroviral therapy (cART) can contribute to accelerated atherosclerosis. cART can lead to metabolic complications such as dyslipidaemia, insulin resistance, and diabetes, which are risk factors for atherosclerosis. Additionally, HIV and associated infections contribute to chronic inflammation, which can also accelerate atherosclerosis.

Pathogenesis of HIV-associated vasculopathy

The pathogenesis of HIV-associated vasculopathy is not yet fully understood. However, it is believed that HIV affects endothelial homoeostasis and function, leading to endothelial dysfunction. This endothelial dysfunction may initiate and propagate atherogenesis and increase the risk of stroke.

Role of cART in the pathogenesis of cerebrovascular disease and stroke

CART may also increase the risk of stroke by accelerating atherosclerosis and increasing life expectancy. While cART is beneficial in treating HIV, it can have adverse effects, including endothelial toxicity and vascular dysfunction, which may contribute to the risk of stroke.

Management of HIV-associated vasculopathy

The management of HIV-associated vasculopathy involves identifying and treating the specific cause of stroke and stroke risk factors, as well as adjusting the cART regimen if necessary. There is a need for further research to optimise the management of HIV-associated vasculopathy and stroke in people living with HIV.

Opportunistic infections

• Herpes simplex virus 1 (HSV-1) infection
• Salmonella infection
• Candidiasis (thrush)
• Toxoplasmosis
• Pneumocystis pneumonia (PCP)
• Tuberculosis

These infections are caused by a variety of germs (viruses, bacteria, fungi, and parasites) and can cause health problems when a person's immune system is weakened by HIV. People with HIV are at greatest risk for opportunistic infections when the count of their infection-fighting CD4 cells falls below 200. However, some opportunistic infections can occur when a person's CD4 count is below 500.

HIV-associated vasculopathy

Aneurysmal Arteriopathy

Most cases of aneurysmal dilation of the cerebral arteries occur in HIV-positive children and young adults. Affected patients develop fusiform or saccular aneurysms, often involving the large blood vessels of the Circle of Willis, and can present with ischemic or hemorrhagic stroke. Pathology is notable for medial fibrosis, damage or loss of the muscularis and internal elastic lamina, and intimal hyperplasia. Later studies indicate that HIV-1 is associated with thinning of the arterial medial layer in autopsied subjects without stroke. The authors suggested that this medial thinning might be a precursor to aneurysmal arteriopathy. Radiologically documented cases of HIV-1 arteriopathy have responded to cART, implicating HIV-1 as a pathogen.

Direct HIV-1 Infection of the Arteries

The ability of HIV-1 to infect vascular cells remains controversial. However, it is agreed that HIV-1 infects other elements in the cerebrovascular milieu, such as perivascular monocytes, macrophages, and astrocytes. Infected cells can release neurotoxic viral proteins such as gp120, Tat, and Nef that damage vascular endothelium and potentially increase the probability of stroke. In vitro, these viral proteins produce changes in vessel morphology, endothelial apoptosis, loss of collagen, loss of membrane glycoproteins, and disruption of the blood–brain barrier. HIV-1 and its viral proteins can also upregulate the expression of chemoattractants, adhesion molecules, and proinflammatory cytokines that damage the blood–brain barrier and increase leukocyte migration into the brain.

Accelerated Atherosclerosis

In the absence of cART, HIV-1 is associated with the development of abnormalities such as increased carotid intimal thickness, carotid arterial wall stiffness, and abnormalities in vascular compliance and distensibility, findings that are associated with atherosclerotic disease. Suppressive cART improves markers of immune activation, inflammation, and coagulation, but elevated levels persist despite effective treatment. HIV-1 may drive atherogenesis through activating endothelial and immune cells, increasing the numbers of circulating atherogenic immune cells, and altering lipid levels and function. The mechanisms by which HIV-1 predisposes the vascular system to atherosclerosis, myocardial infarction, and chronic inflammation have been reviewed and are beyond the scope of this article. Other factors that may contribute to stroke by increasing inflammation and atherosclerosis include coinfection with cytomegalovirus or hepatitis C virus.

Atherosclerosis

HIV can cause atherosclerosis through several mechanisms, including:

• Opportunistic infection
• Vasculopathy
• Cardioembolism
• Coagulopathy

Additionally, antiretroviral therapy (ART) can also increase the risk of atherosclerosis, as it can accelerate the process and increase life expectancy.

Antiretroviral therapy

ART can be administered in the following ways:

• Nucleoside reverse transcriptase inhibitors (NRTIs)
• Non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Protease inhibitor (PI)
• Chemokine receptor 5 (CCR5) antagonist
• Integrase inhibitors (IIs)
• Postattachment inhibitors
• Pharmacokinetic Enhancers

ART has several adverse effects, including:

• Hypersensitivity reaction or rash
• Neutropenia
• Myopathy
• Anemia
• Neuropathy
• Mitochondrial toxicity
• Lactic acid build-up
• Pancreatitis
• Fever
• Rash
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Fatigue
• Achiness
• Shortness of breath
• Sore throat
• Dark-colored urine
• Lipoatrophy
• Jaundice
• Irregular heart rhythm
• Lipodystrophy
• Severe rash
• Jaundice
• Dizziness
• Lightheadedness
• Heartburn
• Fatigue
• Myopathy
• Conjunctivitis
• Mouth sores
• Mouth numbness
• Kidney stones
• Blisters
• Dark-colored urine
• Pancreatitis
• Painful swelling
• Abdominal pain
• Hepatotoxicity
• Kidney failure
• Heart disease
• Diabetes/insulin resistance
• Hyperlipidemia
• Osteoporosis
• Suicidal ideation or depression
• Nervous system deficits

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