Transcript IRIS - HAIVN

Immune Reconstitution
Inflammatory Syndrome
(IRIS)
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
Outline of Presentation
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Definition of IRIS
Pathogenesis of IRIS
Clinical presentation of IRIS
IRIS due to TB, Hepatitis B, CMV
Diagnosis of IRIS
Management of IRIS
Learning objectives
At the end of this presentation, the trainee will be
able to describe:
- The two forms of the Immune Reconstitution
Inflammatory Syndrome (IRIS)
- The etiological agents and syndromes of IRIS
- The management of IRIS
- Commonly encountered forms of IRIS
IRIS: Definition
• IRIS = IRD: Immune Restoration Disease
• IRIS: symptoms or signs consistent with an
inflammatory and/or atypical presentation of
OIs or tumors
– Is not a side effect of ARV,
– Occur after initiation, reintroduction, or change
of ARV
– In patients who have evidence of viral load
suppression.
IRIS: Definition
• IRIS is a pattern of diseases presenting soon
after the initiation of ARV.
• Typically, it occurs in the first 2-12 weeks
after starting ARV.
• IRIS is a “paradoxical” overreaction against
a foreign antigen (alive or dead) in patients
starting ARV.
IRIS: Pathogenesis
• IRIS is secondary
changes after ARV:
to
immunological
– Rapid and potent suppression of HIV viraemia
+
– Abundant microbial antigen (alive or dead)
promotes a greater immune response when it
encounters suddenly increased numbers of
functionally active antigen-specific cells.
IRIS: Clinical presentations
• IRIS in patients already receiving therapy
for an OI at the time at which ARV is
initiated. Clinical deterioration of the
disease: “paradoxical reaction”.
• IRIS may trigger the presentation of an OI
that was sub-clinical prior ARV:
“unmasking IRIS”.
IRIS: Clinical presentations
• Inflammatory response that causes the
unexpected worsening of the patient’s
condition.
• Often there is no detectable evidence of the
underlying pathogen.
• Mycobacterium Tuberculosis accounts for
1/3 of all IRIS events.
• BCG vaccine: very common in infants
Common Pathogens
All infections have been reported to cause IRIS
• Mycobacteria:
– TB and MAC, BCG in children
• Fungal:
– Cryptococcosis, PCP, histoplasmosis, Penicilliosis
• Viral:
– CMV, VZV, HBV, HCV
• Parasites:
– Strongyloides stercoralis, cryptosporidium
IRIS
Risk factors
• Low CD4 count before starting ARV
• Rapid reduction in HIV viral load with ARV
• High pathogen load at the beginning of ARV,
i.e. starting ARV therapy in the setting of an
active OI
• High number of prior OIs
– Minor criteria: increase in CD4 count.
IRIS TB
• Worsening of signs and symptoms of TB in
patients being started on anti-TB chemo-therapy
• Described in the pre-HIV era but appear to be
more frequent in HIV-infected patients
• Occur in 7 to 36% of patients
• More frequently when HAART is started within 2
months of beginning anti-TB treatment
IRIS TB
• Factors complicating
therapy:
ARV
and
– Adherence to heightened pill burden
– Overlapping drug toxicities
– Drug/drug interactions
TB
IRIS TB
• “Paradoxical reaction”:
1. Initial clinical response to TB treatment,
2. ARV introduction,
3. New persistent symptoms or signs of
TB,
4. Adequate adherence to ARV and TB
treatment.
IRIS TB
Diagnosis
• “Paradoxical reaction”:
– Chest X ray/Ultrasound: worsening or new
lesions,
– Good virological response,
– Clear exclusion of other conditions:
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TB treatment failure, resistant TB
others OI,
Malabsortion,
Drug reactions.
IRIS TB
Diagnosis
• “Unmasking IRIS”: Unapparent TB at the
start of ARV
– Insufficient clinical symptoms to justify TB
treatment,
– Chest X ray: normal
– Patients with cough at least 3 sputum: AFB
negative
IRIS TB
Diagnosis
• “Unmasking IRIS”:
– TB appeared within the first 6 months of ARV
– Good virological response to ARV
– Adequate adherence to ARV
CXR before ARV
CXR 3 weeks after ARV
• 8 months old:
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Severe malnutrition
Wt 5 kg; height 58cm
Hepatosplenomegaly
CD4 40.6%; 662 tb/mm3
PCR +
ARV: D4T/3TC/NVP
– enlargement of the axillary
lymph nodes.
IRIS TB
Differential diagnosis
• For patients on TB treatment who develop IRIS
after start ARV: “Paradoxical reaction”
– Side effects of ARV
• drug fevers
– TB infection not responding to treatment
• Resistant TB
• Poor adherence to TB treatment
– Other HIV or non-HIV related infections
• IRIS is a diagnosis of exclusion !!!
Overlapping Side Effects of
Antituberculosis and Antiretroviral Drugs
Overlapping Side Effects of
Antituberculosis and Antiretroviral Drugs
IRIS in Thai children
• Between May 2002-2004 (3 hospital)
– HIV-infected children enrolled: 153
– ARV regimens:
• D4T + 3TC + NVP: 81
• D4T + 3TC + EFV: 72
– Mean Age: 8 years old
– Mean CD4 baseline: 5%
– No active OI
The Pediatric Infectious Disease Journal • Volume 25, Number 1, January 2006
IRIS in Thai children: results
• 153 enrolled children:
– 29 children (19%) had 32 episodes of
IRIS
– Median time: 4 weeks after ARV
• IRIS:
– Mycobacterial: 14 episodes (43%)
• Atypical mycobacteria: 9
• Mycobacterium Tuberculosis: 3
• Mycobacterium Bovis: 2
• Varicella-Zoster: 7 episodes
The Pediatric Infectious Disease Journal • Volume 25, Number 1, January 2006
IRIS in Thai children: results
(cont’)
– HSV: 7 episodes
– Cryptococcus: 3
– Guillain Barre: 1
The Pediatric Infectious Disease Journal • Volume 25, Number 1, January 2006
IRIS in Thai children: outcomes
• One patient interrupted 8 weeks ARV
during IRIS
• 3 patients died of IRIS or its complications
The Pediatric Infectious Disease Journal • Volume 25, Number 1, January 2006
IRIS in infants
(South Africa)
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Infants less than 24 months old: 169
ARV: D4T + 3TC + Aluvia
Median age: 8 months old
IRIS: 34 infants (21%)
– Median time: 2 weeks post-ARV
– BCG disease: 24/34 (71%)
• Local reaction and/or ipsilateral axillary lymph node
AIDS 2009, 23:1097–1107
IRIS in infants
(South Africa)
• Tuberculosis: 12 cases (6 co-infected with
M. bovis)
• Outcomes:
– IRIS: 3/34 died (9%)
• BCG disease: 2 cases
• BCG and TB: 1 case
AIDS 2009, 23:1097–1107
IRIS
Management
• Continuation of primary therapy against the
pathogen,
• Continuation of ARV,
• Judicious use of anti-inflammatory agents,
• To provide reassurance to the patients:
– With appropriate management, IRIS usually
does not alter the patients long-term prognosis.
IRIS
Management
• Corticosteroids (1mg/kg/day) might be necessary in
case of severe symptoms:
– Worsening of meningeal, cerebral or mediastinal disease
with compression of vital structure,
– Pain, prolonged fever.
• In case of life-threatening forms of IRIS, stopping
ARV temporarily could be considered.
* Rifampicin decrease 50% prednisolone concentrations
Managing ARV During IRIS
• Continue ARV
– Except in life-threatening situations
• Adjust for anti-mycobacterial treatment
– If rifampin is prescribed:
• Switch NVP to EFV
• Stop PIs and start EFV or a third NRTI, as
appropriate
• Super boosted PI
Summary and Key Points
• Restoration of immunopathological response to
antigens of opportunistic pathogens
– subclinical infections
– treated infections
• Usually presents during the first weeks (2-12 weeks) of
ARV
• Less commonly presents after many months of ARV
• The most common agent inducing IRIS in Vietnam is
TB/BCG
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Summary and Key Points
• IRIS is a diagnosis of exclusion
• Treatment consists of antimicrobial + antiinflammatory therapy or anti-inflammatory therapy
alone
• IRIS is NOT treatment failure: ARV therapy should
be continued
• The syndrome will be spontaneously resolved after
months
Thank you!
Questions?