1. Stroke In HIV Infection
Dr Prashant Makhija

2. HIV & AIDS
 Family- Human retroviruses (Retroviridae) & subfamily-lentiviruses
 Human immunodeficiency viruses- HIV-1 and HIV-2
 HIV-1- most common cause of HIV disease throughout the world
 HIV-2 - originally confined to West Africa, now identified throughout
the world
 HIV-1- subgroups M, N, O, P
 HIV-2 - subgroups A through G
 The AIDS pandemic is primarily caused by the HIV-1 M group viruses
Harrison’ s Principles Of Internal Medicine. 18th edition. Ch.189

3. Problem Statement
 Joint United Nations Programme on HIV/AIDS (UNAIDS) 2009
Worldwide
 estimated 33.3 million individuals were living with HIV infection
 ~ 50% are female, and 2.5 million (7.5%) are children <15 years
 AIDS deaths- totaled 1.8 million (including 2.6 lakh children <15 years)
India
 estimated number of people living with HIV/AIDS 2.39 million
 ~ 39% are female and 3.5% are children
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1.72 lakh people were reported to have died from AIDS-related causes`

4. CDC classification system for HIV-infection
 Categorizes persons on the basis of clinical conditions associated with HIV
infection and CD4+ T lymphocyte counts
CD4+ T Cell
Categories
A
Asymptomatic,
Acute
(Primary) HIV
or PGL
B
Symptomatic,
Not A or C
Conditions
C
AIDSIndicator
Conditions
>500/µL
A1
B1
C1
200–499/µL
A2
B2
C2
<200/µL
A3
B3
C3
 Once individuals have had a clinical condition in category B, their disease
classification cannot be reverted back to category A, even if the condition
resolves; the same holds true for category C in relation to category B
Harrison’ s Principles Of Internal Medicine. 18th edition. Ch.189

5. Category B: Symptomatic conditions in an HIV-infected
 Bacillary angiomatosis
 Candidiasis, oropharyngeal (thrush) Candidiasis, vulvovaginal; persistent,
frequent, or poorly responsive to therapy
 Cervical dysplasia (moderate or severe)/cervical carcinoma in situ
 Constitutional symptoms, such as fever (38.5 C) or diarrhea lasting >1 month
 Hairy leukoplakia,
 Oral Herpes zoster (shingles), involving at least two distinct episodes or more than
one dermatome
 Idiopathic thrombocytopenic purpura
 Listeriosis
 Pelvic inflammatory disease, particularly if complicated by tuboovarian abscess
 Peripheral neuropathy

6. Category C: Conditions listed in the AIDS surveillance case
definition
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Candidiasis of bronchi, trachea, or lungs ,Candidiasis esophageal
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (>1 month's duration)
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
HIV-related Encephalopathy
Herpes simplex: chronic ulcer(s) (>1 month's duration); or bronchitis, pneumonia, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (>1 month's duration)
Kaposi's sarcoma Lymphoma, Burkitt's (or equivalent term)
Primary Brain Lymphoma
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified
species, disseminated or extrapulmonary
Pneumocystis jiroveci pneumonia
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV

7. Neurologic Diseases in Patients with HIV Infection
 Opportunistic infections
 Toxoplasmosis
 Cryptococcosis
 Progressive multifocal leukoencephalopathy
 Cytomegalovirus
 Syphilis
 Mycobacterium tuberculosis
 HTLV-I infection
 Amebiasis
 Neoplasms
 Primary CNS lymphoma
 Kaposi's sarcoma

8.  Result of HIV-1 infection
 Aseptic meningitis
 HIV-associated neurocognitive disorders, including HIV
encephalopathy/AIDS dementia complex
 Myelopathy
 Vacuolar myelopathy
 Pure sensory ataxia
 Paresthesia/dysesthesia

9.  Peripheral neuropathy
 Acute inflammatory demyelinating polyneuropathy (Guillain-Barré
syndrome)
 Chronic inflammatory demyelinating polyneuropathy (CIDP)
 Mononeuritis multiplex
 Distal symmetric polyneuropathy
 Myopathy

11. STROKE
 Epidemiology
 Epidemiological data differs depending on the population (i.e. industrialized
countries vs. Sub-Saharan Africa) and the date of the study period [i.e.before vs.
after highly active antiretroviral therapy (HAART) implementation]
 The reported rate of stroke occurrence varies between 0.5 and 5% in different
clinical series
 Necropsy studies of HIV-infected subjects have shown a higher prevalence
 Pathological findings- asymptomatic
 Most clinical series consistently show that strokes continue to occur at young
age (< 50 years) in HIV-infected patients
 HIV infection and particularly AIDS appear to be associated with an increased
risk of stroke
Souvik Sen et.al. Recent Developments regarding Human Immunodeficiency Virus Infection and Stroke Cerebrovasc Dis 2012;33:209–218

12. First Author
Population
Method/Study
Period
Rate
Engstrom (1989)
1,600 patients with
AIDS
case series
1982–1987
12 (0.75%)
Connor (2000)
183 necropsies of
HIV cases
necropsy
series
10 (5.5%)
Evers (2003)
772 patients with
HIV
cohort study
1993–2001
15 IS/TIA (1.9%)
Corral (2009)
2,012 patients with
HIV
treated with HAART
case series
1996–2008
27 IS/TIA in 25
patients (1.2%)

13. ISCHEMIC STROKE
 Clinical, radiological, and pathological series, there is an increased risk of IS in
AIDS patients
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South Africa (2000–2006) 67 HIV- infected with Stroke
96% pts. Ischemic strokes
91% were younger than 46 years
opportunistic infections- 37%, most common infection was tuberculosis (15%)
HIV-associated vasculopathy-20%
Cardioembolism- (14%) patients
At the time of their stroke, 46% of these patients had CD4 counts < 200 cells/mm3
Traditional vascular risk factors were uncommon in these HIV-infected patients with
stroke
Tipping B et.al. J Neurol Neurosurg Psychiatry 2007;78:1320–1324

14.  United States (1996-2004) - 82 HIV-infected patients with stroke
 94% had Ischemic Strokes
 Most patients severely immunosuppressed at the time of the stroke
(85% had counts < 200cells/mm3)
 Mechanism - large artery atherosclerosis in 12%, cardiac embolism
in 18%,small artery occlusion in 18%, other determined cause in
23% and cryptogenic in 29%
Ortiz G et. al. Mechanisms of ischemic stroke in HIV-infected patients. Neurology 2007; 68: 1257–1261

15. Potential Causes of Ischemic Stroke in AIDS/HIVInfected Patients
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Cardioembolic
Nonbacterial thrombotic endocarditis
Infective endocarditis
HIV myocarditis
Myxoid valvular degeneration
Mural thrombus
Dilated cardiomyopathy
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Cerebral opportunistic vasculitis/vasculopathy
Cytomegalovirus
Mycobacterium tuberculosis
Varicella-Zoster virus
Syphilis
Cryptococcosis
Mucormycosis
Aspergillosis
Candida albicans
Toxoplasmosis
Coccidioidomycosis
Trypanosomiasis

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Prothrombotic states
Protein S deficiency
Antiphospholipid antibodies
Disseminated intravascular coagulation
HIV-related vasculitis/vasculopathy
Impaired vasoreactivity
Impaired vascular bed-specific homeostasis
Accelerated atherosclerosis with protease inhibitors
Dyslipidemia, insulin resistance
Endothelial dysfunction
Cryptogenic

17. HIV-related Vasculopathy
 Suggested as the mechanism of stroke in HIV/AIDS patients who are
free of other vascular risk factors
 Direct infection of the vessel walls by HIV
 Characterized by small-vessels wall thickening, pigment deposition
with vessel wall mineralization, and occasional perivascular
inflammatory cells infiltrates
 Vascular changes are similar to those found in elderly patients with
vascular risk factors and cerebral atherosclerosis
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

18.  Abnormalities of cerebral perfusion have been documented in
asymptomatic HIV patients using 113Xe single-photon emission
computed tomography
 Suggesting alterations of cerebral resistance at the arteriolar level
 Clinical relevance of HIV-related vasculopathy is still debatable
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

19. HAART Regimen and
HIV-Infected/AIDS Patients
 Pre HAART era- incidence of atherosclerosis was low in HIVinfected pts
 With the introduction of HAART regimen- ↑ incidence of
atherosclerosis
 Mechanisms
 ↑ life expectancy- age related atherosclerosis
 Proatherosclerotic effects of the HIV infection itself
 Metabolic changes resulting from HAART regimen
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

20.  Treatment with PIs has been associated with severe premature
atherosclerotic vascular disease
 Metabolic changes—dyslipidemia, insulin resistance
 Lipid abnormalities may be present in 24 to 64%of patients treated
with PIs
 Studies have preferentially implicated Ritonavir
 Fibric acid derivatives and statins can lower HAART-associated
increases in dyslipidemia- Pravastatin showing least interactions
with PIs
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

21. HEMORRHAGIC STROKE
 ICH is a later complication of HIV infection, generally with CD4 Tlymphocytes cells < 200 mm3
 Studies report conflicting data regarding the incidence of ICH in
HIV-infected pts.
 Cole and coworkers in the first population case-based study found
an incidence of 0.11% per year for ICH with an adjusted RR of
12.7% (95% CI, 4 to 40)
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

22. Potential Causes of Intracerebral Hemorrhage in
AIDS/HIV-Infected Patients
 Opportunistic infection
 Mycobacterium tuberculosis
 Toxoplasmosis
 Opportunistic neoplasm
 Lymphoma
 Metastatic Kaposi sarcoma
 Coagulation/Bleeding disorders
 Disseminated intravascular coagulation
 Thrombocytopenia
 Vascular
 Mycotic aneurysm (IVDA)
Amélia Nogueira Pinto . Semin Cerebrovasc Dis Stroke 5:40-46

23. CVT In HIV Patients
 HIV infected patients are predisposed to venous thrombosis
(Central & Peripheral Vasculature)
 CVT has been reported as presenting feature in HIV-infected
patients
 Clinical presentation and radiological features are similar to dural
venous thrombosis of any cause
M Saravanan et al. Brain: non-infective and non-neoplastic manifestations of HIV. The British Journal of Radiology, 82 (2009), 956–965
Muhammad Wasif Saif et.al. HIV and Thrombosis: A Review. AIDS Patient Care and STDs. January 2001, 15(1): 15-24

24.  Etiology
 Clotting factor abnormalities- deficiencies of protein C, protein S,
heparin cofactor II, and antithrombin
 Antibodies- presence of antiphospholipid antibodies and the lupus
anticoagulant
 Presence of concurrent infectious or neoplastic diseases
 Treatment
 Includes anticoagulation and treatment of the underlying disorder
M Saravanan et al. Brain: non-infective and non-neoplastic manifestations of HIV. The British Journal of Radiology, 82 (2009), 956–965
Muhammad Wasif Saif et.al. HIV and Thrombosis: A Review. AIDS Patient Care and STDs. January 2001, 15(1): 15-24

25. CONCLUSIONS
 Infection with HIV may contribute to an increased risk of stroke
 Strokes tend to occur in young patients with uncontrolled HIV infection and more
severe immunosuppression(CD4 <200/ mm3)
 The most common underlying causes of ischemic stroke- Cardioembolic ,
infectious vasculitis, hypercoaguability and HIV vasculopathy
 Hemorrhagic stroke - coagulation disturbances, thrombocytopenia, intracerebral
tumors or CNS infection
 The widespread adoption of highly active antiretroviral regimens has resulted in a
decrease in the frequency of many of the neurological complications of HIV
 However its effect may be counterbalanced by the proatherosclerotic effects of
Protease Inhibitors

26. THANK YOU