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

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

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.

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*

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 .

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.

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)

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)

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)

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

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

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

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

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

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

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 .

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)

Thanks

• Dr R R Gangakhedkar

• Dr Suresh Ughade

• Dr Urmila Varadpande

• All My patients

• My wife and daughter

• Sanjeevan – Nagpur- India