Is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

1. IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
Presented by:
HAMISI MKINDI,MD4
SFUCHAS

2. INTRODUCTION
Is a condition seen in some cases of AIDS or
immunosuppression, in which the immune
system begins to recover, but then responds to a
previously acquired opportunistic infection with
an overwhelming inflammatory response that
paradoxically makes the symptoms of infection
worse.

3. 3
Risk factors
• Risk factors at base line:
– Lower CD4 count prior to start of ART
– Initiating ART in close proximity to starting therapy
for an OI
• Response to therapy & the development of
IRIS:
– Rapid fall in HIV RNA level during the first 3
months of therapy

4. PATHOGENESIS

5. There are 2 presentations
• Paradoxical IRIS: worsening of symptoms of a
known disease during ART
• Unmasking IRIS: present of an occult
opportunistic infection , in which disease that
was not clinically apparent prior to ART,
manifests during ART

6. Diagnosis
Major criteria
• Atypical presentation of ‘opportunistic
infections or tumours’ in patients responding
to antiretroviral therapy
• Decrease in plasma HIV RNA level by 1log10
copies/mL

7. Diagnosis
Minor criteria
• Increased blood CD4 T-cell count after HAART
• Increase in an immune response specific to
the relevant pathogen.
• Spontaneous resolution of disease without
specific antimicrobial therapy or tumour
chemotherapy with continuation of anti-
retroviral therapy anti-retroviral therapy

8. Paradoxical iris

9. Unmasking IRIS

10. DISEASE SPECIFIC IRIS

11. Disease Specific IRIS
TB IRIS
• The paradoxical reaction that follows the
commencement of anti-TB therapy for pulmonary TB is
usually characterized by fever, malaise, weight loss, and
worsening respiratory symptoms
• Patients with extrapulmonary TB infection may develop
worsening lymphadenitis, new pleural effusions, or
expansion of preexisting intracranial tuberculomas, as
well as a variety of other neurological symptoms after
anti-tuberculosis therapy is begun
• Most occur within 2 months of ART initiation

12. Disease Specific IRIS
MAC IRIS
• In the majority of cases, IRIS due to MAC manifests
as fever and painful lymphadenitis that occurs one to
eight weeks after HAART is commenced
• Individual case reports or small case series also exist
describing IRIS syndrome manifesting as necrotic
subcutaneous nodules, osteomyelitis, bursitis,
granulomatous hepatitis, paravertebral abscesses,
brain abscess, worsening lung infiltrates, or diffuse
intestinal involvement presenting with abdominal
pain

13. Disease Specific IRIS
Cryptococcus IRIS
• IRIS associated with preexisting cryptococcal infection & HIV-
infected patients previously infected with Cryptococcus spp.
may develop symptoms of IRIS localized to the central
nervous system (CNS) or the lungs
• Symptoms often occur within two months after
commencement of therapy, but may be delayed for more
than six months
• Despite the use of concurrent antifungal therapy, patients
with preexisting cryptococcal meningoencephalitis may
develop fever, increased headache, nausea, eye pain,
photophobia, and nuchal rigidity following the initiation of
HAART

14. Disease Specific IRIS
Cryptococcus IRIS
• Repeat lumbar puncture in patients with IRIS associated with
cryptococcal meningitis often reveals more inflammatory cells than
were found prior to the initiation of antifungal therapy and HAART
• Cultures usually remain sterile
• Patients with IRIS-related cryptococcal meningitis had significantly
higher opening pressures, CD4 cell counts, and lower HIV viral loads
• HIV-infected patients with preexisting cryptococcal pulmonary
infection may develop cavitary lung lesions, hypoxia, respiratory
failure, and ARDS following the initiation of HAART
• Rarely, patients with disseminated cryptococcal infections may
develop mediastinal lymphadenitis, hypercalcemia, and cutaneous
abscesses as part of the IRIS syndrome

15. Management
• Proper history:
Time course of symptoms
-History of Ois, recently diagnosed Ois
-Treatment of Ois: date of initiation, adherence, duration and clinical
response
-ART initiation date, specific antiretroviral regimen, medication adherence,
and previous history of ART
-CD4 cell count and HIV viral load before ART initiation
-Current CD4 cell count and HIV viral load, if known
Other medications

16. Management
Diagnostic evaluation:Important to r/o other cond’s before
concluding IRIS
• Complete blood count (CBC) with differential, electrolytes
and creatinine, liver function tests
• CD4 cell count and HIV viral load
• Blood cultures for bacteria, acid-fast bacteria (MAC), fungi
• Chest X ray; other radiographic studies
• Sputum stain and culture
• Biopsy or culture of skin or other lesions
• Lumbar puncture and cerebrospinal fluid studies
• Drug resistance testing for the OI being treated, if indicated

17. Management
Treatement
Best treatment????
Depend on severity
Treatment options
• Observation
• Corticosteroids
• Temporary cessation of ART

18. Prevention
• Patient Education
• Patients starting ART who have CD4 counts of
<100 cells/µL or known concomitant OIs should
be counseled about the possibility of IRIS.
• All patients starting ART should be advised to
contact the clinic promptly if they experience
new or worsening symptoms.
• Advise patients to take their medications for HIV
and for the treatment or prevention of OIs exactly
as prescribed.

20. References
• Centers for Disease Control and Prevention.
Guidelines for Prevention and Treatment of
Opportunistic Infections among HIV-Exposed and
HIV-Infected Children.
• http://en.wikipedia.org/wiki/Progressive_multifo
cal_leukoencephalopathy.
• HIV Medicine book 2006 www.HIVMedicine.com
• 0E_Baylor HIV curriculum 2005complete.
• Journal of Antimicrobial Chemotherapy (2006)
57, 167-170;Samuel A. Shelburne, Martin Montes
and Richard J.Hamill

21. COMMENTS/QUESTIONS/ADDITIONS