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Bhatia IRIS
Bhatia IRIS
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Delan McCullagh
IRIS
Immune Reconstitution Inflammatory Syndrome
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IRIS
• What is it
• How do you recognize it
• Who gets it
• How do you treat it
• Can you avoid it?
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IRIS
• Pathological Inflammatory response and paradoxical clinical
deterioration as a result of HAART related immune recovery or
reconstitution in HIV infected persons
• Also seen in the context of CMV, Cryptococcal Disease and other OIs
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IRIS : Proposed Diagnostic criteria
• Major Criteria
– Atypical presentation of OI or tumours in pts on HAART
– Exaggerated Inflammatory response
• Fever, painful lesions
– Atypical Inflammatory Response In affected tissues
• Granulomas,Suppuration,Necrosis
– Progression of organ dysfunction or enlargement of pre existing
lesions after definite clinical improvement with specific OI therapy
and exclusion of toxicity prior to starting HAART
• Tuberculomas, Worsenng Kaposi’s, New onset CMV retinitis or
CMV uveitis,
– Reduction in Plasma HIV RNA by > 1 log 10 copies /ml
• Minor Criteria
– Increase in CD4#
– Increase in specific immune response to the pathogen
– Spontaneous resolution of disease without specific therapy with
continued anti retroviral therapy
French et al 2004
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Immune reconstitution
inflammatory syndrome (IRIS)
• Case Definition:
– A paradoxical deterioration in clinical
status after initiating highly active
antiretroviral therapy (HAART)
attributable to the recovery of the
immune response to latent or subclinical
infectious or non-infectious processes
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IRIS
• Worsening of original disease
• No evidence of bacteriological relapse or
recurrence*
• May have high fevers – must exclude
concomitant disease
• Related to start of ARV not to OI Rx
• Often prolonged
Microbial Host
antigens susceptibility
CD4< 50
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Antiretroviral Therapy Improves
Qualitative and Quantitative Immune
Defects
Immune suppression/deficiency
Immune Reconstitution
HAART
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Migueles, Buenos Aires 2003
ART and the treatment of OIs
Patient with OI
Treated with
ART
Asymptomatic Return of
New
immune original
Symptoms
recovery symptoms
Medication
Relapse IRIS New OI IRIS
Side-effects
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ART with subclinical infection
ART in
advanced
HIV disease
Asymptomatic
Immune IRIS
recovery
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“Paradoxical Reactions” in Tuberculosis
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“Paradoxical reactions” or IRIS in Tuberculosis and
HIV Co-infection
• More frequent in HIV+ than HIV – patients
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IRIS: TB +HIV
• 27 papers = 86 cases
• Majority of cases of IRIS occurred in pts who were
being treated for TB when HAART initiated
• Fever
• Worsening Lymphadenopathy (71%)
• Increasing respiratory distress
• Deterioration of parenchymal lung
disease (28%)
• New effusions, ascites, abscesses
• Hypercalcaemia, ARF
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Management of IRIS
NO GOOD DATA
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IRIS - HIV and TB
• THERAPY:
– HAART interrupted in ~15% of cases
– Adjunctive therapy
• Corticosteroids (26%)
• Thalidomide
• Pentoxyfylline
• NSAIDS
• Surgery to drain abscesses
• Supportive care
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Prevention
• Screen all patients with advanced HIV disease for
underlying or subclinical infections before starting
HAART
– Significant problem in developing world
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