IRIS

1IRISDr Gulshan Bhatia MRCP(UK) DTMHMedical Director Santa Clara County TB ClinicDivision of Infectious Diseases Santa Clara County Health and Hospital System

12IRIS Immune Reconstitution Inflammatory Syndrome

Delan McCullagh23IRISWhat is itHow do you recognize itWho gets itHow do you treat itCan you avoid it?

34IRISPathological Inflammatory response and paradoxical clinical deterioration as a result of HAART related immune recovery or reconstitution in HIV infected persons

Also referred to as Immune Restoration Disease or Immune Recovery Syndrome

40% of cases reported through 2002 occurred in the context of mycobacterial infections and HIV

Also seen in the context of CMV, Cryptococcal Disease and other OIs

Recognized in HIV seronegative persons experiencing immune recovery

Equivalent to the paradoxical responses seen in patients with TB who are HIV negative ( 2-23% ), 45IRIS : Proposed Diagnostic criteriaMajor CriteriaAtypical presentation of OI or tumours in pts on HAARTExaggerated Inflammatory response Fever, painful lesionsAtypical Inflammatory Response In affected tissuesGranulomas,Suppuration,NecrosisProgression of organ dysfunction or enlargement of pre existing lesions after definite clinical improvement with specific OI therapy and exclusion of toxicity prior to starting HAARTTuberculomas, Worsenng Kaposis, New onset CMV retinitis or CMV uveitis,Reduction in Plasma HIV RNA by > 1 log 10 copies /mlMinor CriteriaIncrease in CD4#Increase in specific immune response to the pathogenSpontaneous resolution of disease without specific therapy with continued anti retroviral therapy French et al 200456Immune 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

67IRISWorsening 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 RxOften prolonged

* NB not always the case78HostsusceptibilityCD4< 50

Microbial antigensRisk factors for IRISAdapted from French et al, 200489Risk Factors for IRISAdvanced HIV disease - CD4 counts