Prepared by the AETC National Resource Center based on recommendations from the CDC, National...

Prepared by the AETC National Resource Center based on recommendations from the CDC,

National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America

Guidelines for Prevention and Treatment of Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults Opportunistic Infections in HIV-Infected Adults and Adolescentsand Adolescents

Progressive Multifocal Leukoencephalopathy Progressive Multifocal Leukoencephalopathy (PML) Slide Set(PML) Slide Set

May 2013 www.aidsetc.org2

About This PresentationAbout This Presentation

These slides were developed using recommendations published in May 2013. The intended audience is clinicians involved in the care of patients with HIV.

Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 Resource Center

http://www.aidsetc.org


PML: PML: EpidemiologyEpidemiology

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


PML: PML: Epidemiology Epidemiology (2)(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)


PML: PML: Clinical ManifestationsClinical 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


PML:PML: Diagnosis Diagnosis

Compatible clinical syndrome and radiographic findings allow presumptive diagnosis in most cases Clinical: steady progression of focal

neurological deficits

Imaging: MRI is preferred


PML:PML: Diagnosis Diagnosis (2)(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


PML:PML: Diagnosis Diagnosis (3)(3)

PML, CT scan PML, MRI scan

Credit: Images courtesy AIDS Images Library (www.aids-images.ch)


PML: PML: Diagnosis Diagnosis (4)(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, butnewer approaches under investigation


PML: PML: PreventionPrevention

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


PML:PML: Treatment 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


PML:PML: Treatment Treatment

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


PML:PML: Starting ART Starting ART

ART should be started immediately upon diagnosis of PML

For persons on ART with HIV viremia, optimize ART to achieve HIV suppression


PML:PML: Monitoring and Adverse Events 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


PML: PML: Monitoring and Adverse Events Monitoring and Adverse Events (2)(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


PML:PML: Monitoring and Adverse Events Monitoring and Adverse Events (3)(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


PML:PML: Treatment Failure 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”)


PML:PML: Preventing Recurrence Preventing Recurrence

Effective ART regimen


PML:PML: Considerations in Pregnancy Considerations in Pregnancy

Diagnosis as in nonpregnant adults

Treatment: optimal ART


Websites to Access the GuidelinesWebsites to Access the Guidelines


http://aidsinfo.nih.gov


This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in May 2013

See the AETC NRC website for the most current version of this presentation:


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