CLINICAL

• Paradoxical deterioration in clinical status after ART initiation despite improved immune function due to inflammatory response against infectious antigen, which may or may not have been Dx’d at initiation of ART
  • Paradoxical IRIS refers to inflammation related to a known underlying infectious or non-infectious antigen
  • Unmasking IRIS refers to inflammation leading to the diagnosis of a condition that was present but not known at the time of ART initiation
• Typically occurs in pts with low initial CD4 (usually < 50) and rapid decline in viral load; onset usually within 6 wks of ART initiation, but sometimes several mos later. Later presentation includes several mos after tx of cryptococcal meningitis and some autoimmune related conditions (Grave’s disease).
• Up to 50% of pts starting ART with CD4 < 50 c develop some form of IRIS (often mild)
• Inciting pathogens: M. avium complex, M. tuberculosis, and other mycobacteria, CMV, Cryptococcus, Pneumocystis jiroveci, Leishmania, HSV, VZV, hepatitis B and C, JC virus, HHV8 (Kaposi’s and Castleman’s), JC virus (PML), and others.
• Common Sx (varies according to causative pathogen): fever, localized lymphadenophathy/lymphadenitis, abscesses, pneumonia, vitritis, CNS disease, hepatitis, mass effects, and dermatologic manifestations including eosinophilic folliculitis.
• Presentations of OIs may be atypical (eg, MAC: localized granulomatous lymphadenopathy without mycobacteremia; CMV: vitritis; PML: enhancing CNS lesions; Cryptococcus: marked CSF leukocytosis).
• Autoimmune diseases (e.g.sarcoidosis, Grave’s disease) may be exacerbated after starting / restarting ART
• Despite high risk (>25%) of paradoxical worsening in pts with active TB after initiation of ART, overall mortality reduced in pts with CD4 < 100 treated with ART and TB therapy.