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field of HIV care, this information could become out of date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
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
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
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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