Can HIV increase the risk of stroke?

Yes, HIV infection is associated with an increased risk of stroke. Studies have shown that people living with HIV have a higher likelihood of experiencing stroke compared to the general population.

Are there any specific considerations for managing stroke in HIV-positive individuals?

Yes, managing stroke in HIV-positive individuals may require additional considerations, including potential drug interactions between antiretroviral medications and medications used to treat stroke, as well as addressing underlying HIV-related complications such as opportunistic infections or coagulopathies.

ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS

Stroke and HIV infection

David Goldemund M.D.
Updated on 21/02/2024, published on 19/02/2024

human immunodeficiency virus (HIV) attacks a group of white blood cells called CD4+ T lymphocytes (also known as helper cells), in which the virus replicates and later kills them, reducing their number in the infected person’s body
HIV infection is associated with an increased risk of stroke (most commonly ischemic)
however, it is not clear how often stroke occurs by chance and how often there is an actual causal relationship with the infection, its complications, or antiretroviral therapy (ART) (particularly protease inhibitors can contribute to atherogenic lipid profiles) (Benjamin, 2016)
a variety of mechanisms leading to stroke has been postulated, including opportunistic infections, cardio-thromboembolism, coagulopathy, and the incompletely understood HIV-associated vasculopathy

Etiopathogenesis

Primary HIV vasculopathy

small-vessel vasculopathy (SVD)
- characterized by hyaline thickening of the arteriolar wall
- SVD may play a role in HIV-associated neurocognitive disorders
HIV-associated vasculopathy
- accelerated atherosclerosis in extra- and intracranial arteries
  - atherosclerosis is accelerated in HIV populations, occurring up to 2 decades earlier than expected (Benjamin, 2016)
  - chronic inflammation caused by incomplete HIV suppression or dyslipidemia associated with some HIV treatments is believed to be the underlying mechanism
- nonatherosclerotic vasculopathy
  - intimal hyperplasia in the absence of atherosclerosis or vasculitis
  - formation of fusiform intracranial aneurysms [Goldstein, 2009]

HIV-associated vasculitis

a relatively rare complication of HIV infection
the exact prevalence is difficult to ascertain due to the varied clinical manifestations and the overlap with other conditions that can affect the vasculature in HIV-infected individuals
vessels of all sizes may be affected; a single organ vasculitis is common (such as limited to the brain)
vasculitis can either be caused by infection (such as VZV) or by noninfectious immune-mediated mechanisms
a biopsy of affected tissue, when accessible and safe to obtain, is the gold standard for diagnosing vasculitis
- histopathological examination can reveal inflammation, fibrinoid necrosis, and infiltration of the vessel wall by immune cells

Prothrombotic condition

coagulopathy (protein C and S deficiency)
- usually associated with venous thrombosis, not with arterial stroke
hyperviscosity syndrome
antiphospholipid syndrome
venous thrombosis provoked by cachexia and dehydration

Other causes

cardioembolism (due to cardiomyopathy, endocarditis, and nonbacterial endocarditis)
stroke related to opportunistic infections
- herpes simplex virus
- varicella zoster virus (VZV)
- cytomegalovirus
- tuberculosis
- toxoplasmosis
- fungal infections (e.g., cryptococcosis, aspergillosis, nocardiosis, histoplasmosis, etc)
secondary malignancies propagating into the vascular system (lymphomas)
protease inhibitors-related accelerated atherosclerosis [Vittecoq, 1998]

Diagnostic evaluation

Diagnosis of HIV infection

diagnosis of HIV typically involves a combination of clinical assessment and laboratory testing
medical history and physical examination (including risk factors for HIV transmission and symptoms suggestive of acute HIV infection or advanced HIV disease)
HIV antibody testing
CD4+ T-cell count
- monitoring the CD4+ T-cell count and HIV viral load helps assess disease progression and guide treatment decisions
- a low CD4+ count indicates immunosuppression, which increases the risk of opportunistic infections and other HIV-related complications
screening for other STDs (Sexually Transmitted Diseases), such as syphilis, gonorrhea, and chlamydia

Etiopathogenetic evaluation of stroke

HIV vasculopathy is a diagnosis by exclusion
the presence of HIV in a young stroke patient warrants a full diagnostic workup, as HIV infection may be incidental
look for opportunistic infections, tumors, and drug abuse
patients with HIV should be screened for neurosyphilis (and vice versa)
a detailed cardiological examination, including TEE, is essential

HIV tests

specific HIV antibody tests (immunoassays)
- occurring in almost 100% of HIV-infected individuals within 3 weeks to 3 months of infection
  - HIV enzyme immunoassay or rapid HIV test
  - confirmed with Western blot, antigen test, or PCR
- the test may be falsely negative in the early post-infection period when antibodies have not yet formed ⇒ for epidemiologic or clinical suspicion; the test should be repeated in 2-3 months
HIV RNA test (aka Nucleic Acid Tests) – directly detects the presence of HIV RNA in the blood
- highly sensitive and can detect HIV earlier than antibody tests
fourth-generation HIV test – detects both HIV antibodies and p24 antigen
- p24 is a protein antigen that is part of the viral capsid; its detection is particularly useful in the early stages when antibody levels are still absent or low

Other blood tests

CBC + coagulation tests + basic metabolic panel
antiphospholipid antibodies (LA, ACLA, anti-β2 GB)
treponemal tests (immunoassay + agglutination test)
- nontreponemal tests (detect total antibodies, used for screening):
  - Venereal Disease Research Laboratory (VDRL) test
  - Rapid Plasma Reagin (RPR) test
- treponemal tests (confirmatory tests) → more here
  - treponema pallidum particle agglutination assay (TP-PA)
  - enzyme immunoassay (EIA)
  - Fluorescent Treponemal Antibody Absorption (FTA-ABS) test
VZV-IgG and IgM
blood cultures in febrile patients
ADAMTS13 levels and antibodies
hepatitis B+C tests

CSF

cytology
glucose + protein
standard bacterial cultures
cryptococcal and TB cultures (if CD4+< 200 cells/mm³ or CSF WCC > 20 / mm³)
VZV-IgG index and PCR → varicella zoster virus vasculopathy
VDLR (if blood syphilis screen is positive)
cryptococcal antigen (if CD4+ < 200 cells/mm³ or CSF WCC > 20 / mm³)

Stroke mimics

infection (toxoplasma, progressive multifocal leukoencephalopathy, viral encephalitides, fungal infections)
lymphoma
HIV-associated tumefactive demyelination

Management

Acute stroke therapy

recanalization therapy for all eligible patients
antithrombotic drugs for the rest

Stroke prevention

standard stroke prevention
- antiplatelets or anticoagulants based on identified etiology (AHA/ASA 2021 Class 2a/Level of Evidence: C-LD)
  - when selecting antithrombotic therapy for stroke prevention in HIV-positive patients, clinicians must consider potential drug-drug interactions with ART
- management of vascular risk factors
antiviral therapy leads to normalization of CD4+ T-cell count
- therapy may sometimes paradoxically increase the risk of stroke due to) immune reconstitution inflammatory syndrome (IRIS) + some ART regimens may increase cardiovascular risk factors, such as dyslipidemia [Newsome, 2009]

HIV-vasculitis

appropriate ART + immunosuppressive therapy tailored to the severity of the vasculitis and the organs involved
collaboration with specialists in rheumatology, infectious diseases, and other relevant fields is essential for comprehensive care