Transcript PML

Guidelines for Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents
Progressive Multifocal
Leukoencephalopathy Slide Set
Prepared by the AETC National Coordinating Resource Center based on
recommendations from the CDC, National Institutes of Health, and HIV
Medicine Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in July 2013. The intended audience is clinicians
involved in the care of patients with HIV. Certain sections
have been updated to reflect changes in the published
guidelines.
Users are cautioned that, because of the rapidly changing
field of HIV care, this information could become out of date
quickly. Finally, it is intended that these slides be used as
prepared, without changes in either content or attribution.
Users are asked to honor this intent.
– AETC National Coordinating Resource Center
http://www.aidsetc.org
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Progressive Multifocal
Leukoencephalopathy
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Epidemiology
Clinical Manifestations
Diagnosis
Preventing Disease
Treatment
Monitoring
Preventing Recurrence
Considerations in Pregnancy
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PML: Epidemiology
 Opportunistic infection, caused by the polyoma virus JC
virus
 Characterized by focal demyelination in the CNS
 Worldwide distribution, seroprevalence of 39-69% in
adults
 Primary infection usually in childhood
 No recognized acute JC virus infection
 Likely asymptomatic chronic carrier state
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PML: Epidemiology (2)
 Before use of potent ART, PML developed in 3-7% of
persons with AIDS
 Substantially lower incidence in countries with wide
access to ART
 High mortality rate
 Usually occurs with low CD4 count, but may occur with
CD4 count >200 cells/μL and in those on ART
 Rarely occurs in HIV-uninfected immuno-compromised
persons
 Reported in persons treated with immunomodulatory
humanized antibodies (eg, natalizumab, efalizumab,
infliximab, rituximab)
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PML: Clinical Manifestations
 Focal neurologic deficits, usually with insidious onset, steady
progression over several weeks/months
 Demyelinating lesions may involve any region of the brain
 Common: occipital lobes (hemianopsia), frontal and parietal lobes
(aphasia, hemiparesis, hemisensory deficits), cerebellar peduncles
and deep white matter (dysmetria, ataxia)
 Spinal cord involvement is rare
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Lesions often multiple, though one may predominate
Headache and fever not characteristic (except in severe IRIS)
Seizures in 20%
Cognitive dysfunction may occur but diffuse encephalopathy or
dementia is rare
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PML: Diagnosis
 Compatible clinical syndrome and radiographic findings
allow presumptive diagnosis in most cases
 Clinical: steady progression of focal neurological deficits
 Imaging: MRI is preferred
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PML: Diagnosis (2)
 MRI distinct white matter lesions in brain areas
corresponding to clinical deficits
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Usually hyperintense on T2 and FLAIR, hypointense on T1
Usually no mass effect
Contrast enhancement in 10-15% but usually sparse
IRIS PMN may have different appearance
 Diffusion-weighted imaging and MR spectroscopy may
give additional diagnositic information
 CT scan: single or multiple hypodense, nonenhancing
white matter lesions
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PML: Diagnosis (3)
Credit: Images courtesy AIDS Images Library (www.aids-images.ch)
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PML: Diagnosis (4)
 Definitive diagnosis: valuable, especially for atypical
cases
 CSF evaluation for JC virus DNA (by PCR): helpful if
positive; 70-90% sensitive in patients who are not on ART
(lower in those on ART)
 Brain biopsy: identification of JC virus; visualization of
oligodendrocytes with intranuclear inclusions, bizarre
astrocytes, lipid-laden macrophages
 Serologic testing generally not useful, but
newer approaches under investigation
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PML: Prevention
 Preventing exposure
 No known way to prevent exposure
 Preventing disease
 ART is the only effective way to prevent PML
 Prevention of progressive immunosuppression caused by HIV
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PML: Treatment
 No specific therapy
 Main approach: ART to reverse immune suppression
 Start ART immediately for those not on ART; optimize ART
in all on ART without suppression of HIV viremia
 Effectiveness of ARVs with better CNS penetration is not
established – likely that systemic efficacy is most important, via
restoration of anti-JCV immunity
 Effective ART stops PML progression in approximately 50%
 Neurologic deficits often persist
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PML: Treatment (2)
 Targeted treatments: no proven effective therapies
 Cytarabine, cidofovir: studies show no clinical benefit; not
recommended
 5HT2a receptor inhibitors: clinical trial data lacking; cannot
be recommended
 Interferon-alfa: no clinical benefit; cannot be recommended
 Topotecan: limited data; not recommended
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PML: Starting ART
 ART should be started immediately upon diagnosis of
PML
 For persons on ART with HIV viremia, optimize ART to
achieve HIV suppression
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PML: Monitoring and Adverse Events
 Monitor treatment response with clinical exam and MRI
 If detectable JCV DNA in CSF before ART, may repeat
quantitation of CSF JCV to assess treatment response
(no clear guidelines)
 If stable or improving, repeat MRI 6-8 weeks after ART
initiation
 If clinical worsening, repeat MRI promptly
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PML: Monitoring and Adverse Events (2)
 PML IRIS (inflammatory PML)
 PML may present within first weeks/months after ART
initiation, associated with immune reconstitution
 Both unmasking of cryptic PML and paradoxical worsening of
known PML may occur
 Features may be atypical, may include mass effect,
edema, contrast enhancement on MRI, more rapid
clinical course; perivascular mononuclear inflammatory
infiltration on histopathology
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PML: Monitoring and Adverse Events (3)
 IRIS management:
 Corticosteroids may be helpful if substantial inflammation,
edema or mass effect, or clinical deterioration
 Dosage not established; consider starting with 3- to 5-day
course of methylprednisolone 1 g IV QD, followed by
prednisone 60 mg PO QD tapered over 1-6 weeks, according
to clinical response
 Contrast-enhanced MRI at 2-6 weeks – document status of
inflammation and edema
 ART should be continued
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PML: Treatment Failure
 Clinical worsening and detection of JCV (without
significant decrease) at 3 months
 Optimize ART, if detectable HIV RNA and poor CD4
response
 Consider unproven therapies (see “Treatment”)
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PML: Preventing Recurrence
 Effective ART regimen
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PML: Considerations in Pregnancy
 Diagnosis as in nonpregnant adults
 Treatment: optimal ART
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa Coffey, MD,
for the AETC National Resource Center in July 2013.
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
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