Outline the features of the Immune Reconstitution Inflammatory Syndrome (IRIS) in patients with Human Immunodeficiency Virus (HIV) infection with regards to:
A collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious process following initiation of antiretroviral therapy primarily in HIV-infected patients. It has also been described in patients receiving therapy for TB.
HIV infection produces CD4+ T cell immune suppression.
HIV half-life is generally between 1-4 days
With commencement of antiretroviral therapy there is greater than 90% reduction of HIV viral burden within 1-2 weeks.
CD4+ T lymphocyte count rapidly increases over the first 3-6 weeks
Increased lymphocyte activity then leads to systemic or local inflammatory reactions at the site or sites of pre-existing infection (known or unknown)
Lower CD4 counts at time of initiation of therapy
High viral load at time of initiation of therapy
More significant response to antiretroviral therapy
Progression of initial opportunistic infection
New opportunistic infection
Most patients develop symptoms within 1 week to a few months after the initiation of antiretroviral therapy. Symptoms can be localised or systemic. Features are similar to the primary infection.
Depend on the site and organism involved. Commonly:
Pneumocystis jerovicii: fever, cough, dyspnoea, hypoxia and progressive radiographic pulmonary opacification. BAL: large numbers of inflammatory cells
Cryptococcus: CNS: fever, headache, neck stiffness, photophobia. Pulmonary: lung lesions, hypoxia, respiratory failure and ARDS
TB: clinical or radiological pulmonary deterioration, lymphadenopathy, enlarging intracranial lesions
Others (any reasonable description OK): TB, MAC, CMV (uveitis), JC virus, Hepatitis B&C – worsened LFT’s. with fevers, seats anorexia; Kaposi sarcoma, toxoplasmosis (CNS)
Continue antiretroviral therapy
Treat the underlying opportunistic infection
Severe symptoms = steroid therapy
The college definition seems to be paraphrased from the opening paragraphs of Sharma & Soneja (2011), where it is described as a "paradoxical worsening of an existing infection or disease process". Suggested definitions (French et al, 2004; Robertson et al, 2006) generally require some combination of the following features:
Obviously such HIV-centric definitions do not take into account the fact that IRIS can occur in several other conditions (eg. with tuberculosis).
Pathogenesis of IRIS is well-described in the IRIS article from UpToDate, from which the college answer appears to draw most of its inspirations. For the purposes of regurgitating a point-form summary of what happens, the causes of IRS can be summarised thus:
Risk factors for IRS (according to Shellburn et al, 2005) include:
Differential diagnosis (From Beshuizen et al, 2009):
Clinical manifestations may include:
Management of IRIS (from Konishi et al, 2010)
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Sharma, Surendra K., and Manish Soneja. "HIV & immune reconstitution inflammatory syndrome (IRIS)." The Indian journal of medical research 134.6 (2011): 866.
French, Martyn A., Patricia Price, and Shelley F. Stone. "Immune restoration disease after antiretroviral therapy." Aids18.12 (2004): 1615-1627.
Robertson, Jaime, et al. "Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy." Clinical infectious diseases 42.11 (2006): 1639-1646.
Shelburne, Samuel A., et al. "Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy." AIDS 19.4 (2005): 399-406.
Beishuizen, S. J., and S. E. Geerlings. "Immune reconstitution inflammatory syndrome: immunopathogenesis, risk factors, diagnosis, treatment and prevention." Neth J Med 67.10 (2009): 327-331.
Konishi, M., K. Uno, and E. Yoshimoto. "Management of immune reconstitution inflammatory syndrome." Nihon rinsho. Japanese journal of clinical medicine 68.3 (2010): 508-511.
Richaud, Clémence, et al. "Anti-tumor necrosis factor monoclonal antibody for steroid-dependent TB-IRIS in AIDS." Aids 29.9 (2015): 1117-1119.
Lwin, Nilar, Michael Boyle, and Joshua S. Davis. "Adalimumab for corticosteroid and infliximab-resistant immune reconstitution inflammatory syndrome in the setting of TB/HIV coinfection." Open forum infectious diseases. Vol. 5. No. 2. US: Oxford University Press, 2018.