Strokes And Aids: Understanding The Connection And Risk Factors

Stroke is a serious, life-threatening medical condition that can be caused by a blocked artery (ischaemic stroke) or the leaking or bursting of a blood vessel (haemorrhagic stroke). The most common type is an ischaemic stroke. People living with HIV are at a higher risk of having a stroke, particularly an ischaemic stroke, and at a younger age. This is thought to be due to the impact that HIV has on the body, including chronic inflammation, which can contribute to the hardening of arteries. HIV and opportunistic infections can also cause changes to blood vessels.

The risk of having a stroke seems to be higher if you have a low CD4 count, or if you have HIV and hepatitis C at the same time. Some people also develop a condition called immune reconstitution inflammatory syndrome (IRIS) within the first few months of taking anti-HIV medication, which can affect the brain and increase the risk of an ischaemic stroke. Opportunistic infections such as tuberculosis, meningitis, neurosyphilis and varicella-zoster virus vasculitis can also increase the risk of having a stroke.

Some anti-HIV medications have been linked to an increased risk of stroke, but the benefits of taking anti-HIV medication far outweigh this risk. Some studies have found that abacavir is linked to an increased risk of stroke, heart attack and heart disease. It is not known for sure why this link might exist.

HIV-associated vasculopathy

Several studies have found an association between HIV infection and stroke, particularly ischaemic stroke. HIV-associated vasculopathy is thought to be one of the mechanisms by which HIV infection can lead to stroke.

The standard treatment for HIV, combination antiretroviral therapy (cART), may also contribute to the risk of stroke. cART can accelerate atherosclerosis and increase life expectancy, thereby increasing the risk of stroke.

Opportunistic infections, such as tuberculosis, meningitis, neurosyphilis, and varicella-zoster virus vasculitis, can also increase the risk of stroke in people living with HIV.

Opportunistic infections

A weakened immune system increases vulnerability to opportunistic infections, cancers, and other conditions. The following are some of the more common opportunistic infections:

• Candidiasis, a fungal infection in your mouth, throat, or vagina
• Cryptococcus neoformans (crypto), a fungus that can lead to meningitis, a serious inflammation of the membranes that surround your brain and spinal cord
• Cryptosporidiosis and microsporidiosis, infections of microscopic animals called protozoa that mess up your gut
• Cytomegalovirus (CMV), a virus that causes eye disease and can lead to blindness, severe diarrhea, and ulcers
• Herpes simplex, a group of viruses that cause sores around your mouth and on your genitals
• Mycobacterium avium complex (MAC), bacteria that cause fever, problems with digestion, and serious weight loss
• Pneumocystis pneumonia (PCP), a fungal pneumonia that can be fatal if it’s not diagnosed and treated early
• Progressive multifocal leukoencephalopathy (PML), a virus that affects your brain
• Tuberculosis (TB), a bacterial infection that attacks your lungs and can also invade other organs and lead to meningitis

The best way to prevent opportunistic infections is to take your HIV medicines and keep your CD4 count from becoming low. If you are starting with a low CD4 count, you can take steps to lower your chances of getting these infections.

Coagulopathies/thrombophilias

Protein S is a vitamin K-dependent anticoagulant. Decreased levels or impaired function of protein S leads to a propensity for venous thrombosis. In an HIV-positive African cohort, protein S deficiency was the most common coagulopathy associated with stroke. However, subsequent studies indicated that protein S deficiency is related to HIV serostatus and is not causally related to stroke.

Protein C deficiency is associated with an increased incidence of venous thromboembolism, whereas little association with arterial thrombosis has been found in any group.

Infectious vasculitis is a known cause of stroke. HIV-1 has been linked to the induction of anticardiolipin antibodies, antiphospholipid antibodies, and antiprothrombin antibodies. However, studies in the HIV-negative population suggest that anticardiolipin antibodies are a risk factor for thrombosis and stroke, acting by impairing the activity of the polypeptide tissue factor pathway inhibitor.

Direct HIV-1 infection of the arteries

HIV-1 can directly infect arterial walls, which can lead to stroke. HIV-1 has been found to directly affect vascular biology, resulting in an increased risk of cardiovascular disease compared to uninfected persons. HIV-1 can infect vascular cells, such as perivascular monocytes, macrophages, and astrocytes. Infected cells can release neurotoxic viral proteins such as gp120, Tat, and Nef, which damage vascular endothelium and potentially increase the probability of stroke. 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

Combination antiretroviral therapies (cART) are clearly beneficial, but they can also be atherogenic and could increase stroke risk. cART can prolong life, increasing the size of the ageing population at risk of stroke.

The risk of stroke in patients with HIV and the need for further research to clarify burden, causes, pathogenesis, and management continues in areas with little or inadequate antiretroviral therapy. Equally, the need exists in high-income regions with patients on long-term antiretroviral therapy. The added stroke burden to patients and health services in all regions might only be realised in future decades.

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