the study of immune reconstitution inflammatory syndrome(iris) in resource limited settings
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The study of immune reconstitution inflammatory syndrome(IRIS) in resource limited settings. Dr Milind Bhrushundi M D Dr Pradeep Mishra M D Lata Mangeshkar Hospital Nagpur India. Objectives. - PowerPoint PPT PresentationTRANSCRIPT
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The study of immune reconstitution inflammatory
syndrome(IRIS) in resource limited settings
Dr Milind Bhrushundi M DDr Pradeep Mishra M D
Lata Mangeshkar Hospital NagpurIndia
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Objectives
• To assess proportion of patients developing IRIS after initiation of antiretroviral therapy attending Lata Mangeshkar Hospital (LMH) in Nagpur, India
• To describe pattern of IRIS
• To identify factors associated with development of IRIS
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Methods
• 720 consecutive patients attending LMH, Nagpur between 2002- 2005 were recruited
• Patients were examined clinically & investigated for presence of OI before initiating ART & treated wherever necessary
• Since patients had to pay for complete/ part of tests, package of investigations differed.
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Investigations
Essential Optional Ideal
HIV Serology (NACO)
C B C
CD4+
Chest X-ray
SGPT
Pregnancy Test
Serum Chemistry
VDRL
MantouxTest (5TU)
Hepatitis B
USG Abdomen
CMV IgG
Hepatitis A& Hepatitis C
Toxoplasma IgG
Lipid Profile
Viral load*
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Case definition
• Appearance of new OI or deterioration in patients treated for OI who showed signs & symptoms of clinical improvement initially within 3 months of initiating ART with increase in CD4+ counts
• Worsening of the symptoms without significant rise in CD4+ T-helper were excluded by the definition .
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Demographic profile n=720
• Age- Mean- 35.6 years ( range; 21-75 yrs)• Sex- 582 Males and 138 females• Baseline Investigations: Essential – 230 (32%);
Optional -366 (51%), Ideal - 124 (17%) • Of them, 549 (76%) were ARV-naïve.• Of the 171 ARV-experienced patients, 26 (17%)
had received two ARVs & 143 (83%) received 3 ARVs
• Of the ARV-naïve patients, 71 ( 13%) received EFV-based regime & remaining received NVP-based regimen.
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Results
• Univariate analysis revealed– IRIS was not associated with any age group
(p=0.06)– However, females were found to be less likely
to develop IRIS (p=0.001)– Patients who were offered essential (minimal
tests) package at baseline were more likely to develop IRIS (p= 0.001)
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Results
– Patients with CD4 < 50 cells & between 50-100 cells/cm were likely to develop IRIS (p=0.0001)
– Patients with past history or current OI were more likely to develop IRIS (p=0.0001)
– Patients with CD4 counts of <50 cells were 40 times more likely to develop IRIS. (p= .0001),CD4 counts of <100 cells were 12 times more likely to develop IRIS. (p= 0.0001)
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Results
• Multivariate analysis revealed that the likelihood of development of IRIS was;– Males were 3.1 ( 95% CI – 0.92-11.1) times
more likely to develop IRIS than females. (P=0.06)
– Patients with CD4 counts of <50 cells were 4.3 times more likely to develop IRIS. (p= 0.0001)
– Those who could only afford a minimal (essential) package of base line laboratory tests were 1.4 times more likely to develop IRIS (p=0.05)
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4210
8
4 2 1 1
TB (61.76%) PCP (14.7%)
Cryptococcal meningitis (11.76%) CMV retinitis (5.88%)
Toxoplasma encephalitis (2.94%) Hepatitis C (1.47%)
PML* (1.47%)
Patterns of IRIS
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14
76
5
3
31 1 1 1
ABDOMEN (33.33%) CERVICAL (16.16%)
PTB (14.28) PLEURAL EFFUSION (11.9%)
ABDOMEN ,CERVICAL (7.14%) TBM (7.14%)
PERICARDIAL EFFUSION (2.38%) ABDOMEN CERVICAL INGUINAL (2.38%)
INGUINAL (2.38%) ABDOMEN PSOAS (2.38%)
Patterns of TB IRIS
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DIAGNOSIS OF IRIS CASES PRIOR TO ART
DIAGNOSIS NUMBER %
TB 38 54.41
ENTERIRIS+OEC+OC 19 27.94
ART FAILURE 03 4.41
PCP 03 4.41
CMV RETINITIS 1 01.47
TOXOPLASMA ENCEPHILITIS 1 01.47
CRYPTO MENINGITIS 1 01.47
THALLESEMIA 1 01.47
THROMBOCYTOPENIA 1 01.47
TOTAL 68 100
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CORRELATION OF AKT REGIMEN
Past history of TB Number %
No 30 44.12
Yes 38 55.88
Total 68 100
PRIOR TB
TB IRIS % OTHER IRIS %
DOTS 20 13 65 7 35
2EHRZ/HR 17 13 76.47 4 23.52
2EHRZ/HRX9
01 00 00 1 100
TOTAL 38 26 68.42 12 28.94
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Treatment of IRIS
• TB-DOTS,NVP changed to EFV• PCP- TMP/SMX, Steroids used in 3 cases,
one mortality• Cryptococcal Meningitis-Amphotericin-B,
one mortality, two had Amphotericin toxicity• CMV retinitis- Rx not affordable-Optic
Atrophy, otherwise normal.• Hepatitis C- Pegylated interferon+ Ribavarin• PML-ART, Still having neurological
symptoms
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FOLLOW-UP IRIS CASES
Follow up Number %
On regular follow up 62 91.18
Lost to follow up 4 5.88
Died 2 2.94
Total 68 100
Mortality
Cases IRIS Initial CD4+ CD4 on deterioration
1 Cryptococcal meningitis
13 70
2 PCP 12 78
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Conclusions
• IRIS occurred in 9.4% patients initiated on ART in Nagpur India
• All those who have developed IRIS had prior history of OI
• Limited investigations prior to initiation of ART is associated with increased risk of IRIS
• Proportion of IRIS is less in Government run free ART clinic because of strict protocol for the investigation prior to ART .
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Conclusion
• Proportion of cases is significantly high with low baseline CD4+ counts(<50)
• % increase in CD4+ cells was significantly high (192%) with low CD4+
• Tuberculosis continues to predominate in IRIS in India (in 54% cases)
• Need to educate the Physicians for proper ART(16.66% were on double drug therapy)
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Thanks
• Dr R R Gangakhedkar
• Dr Suresh Ughade
• Dr Urmila Varadpande
• All My patients
• My wife and daughter
• Sanjeevan – Nagpur- India