Immune Reconstitution Inflammatory Syndrome: Opening Pandora’s Box

Abstract

One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm3 (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with severe sepsis. The diagnostic pathway identified progressive multifocal leukoencephalopathy, digestive Kaposi sarcoma, and P. aeruginosa bacteraemia. Five weeks after starting ART, TCD4+ cell count was 259 cells/mm3 (15%) and HIV RNA = 3500 copies/mL (4 log). He developed respiratory failure and progressed to septic shock and death. Those complications might justify the outcome but its autopsy opened Pandora's box: cerebral and cardiac toxoplasmosis was identified, as well as hemophagocytic syndrome, systemic candidiasis, and Mycobacterium avium complex infection. IRIS remains a concern and eventually a barrier to ART. Male gender, young age, low TCD4 cell count, and high viral load are risk factors. The high prevalence of subclinical opportunistic diseases highlights the need for new strategies to reduce IRIS incidence.

A Cross-Sectional Study of Cryptococcal Antigenemia in Anti-Retroviral Naive Hiv Infected Patients

“…Fifteen (15/100) of them were positive for cryptococcal antigen ( Table 1). The CD4 counts in this study ranged from 121 -978 cells/mm 3 and the median CD4 count was 564 cells/mm 3 …”

“…20 While in the present study, 40% of HIV patients with Cryptococcal antigenemia had CD4 counts below 350 cells/mm 3 . But as per WHO recommendations, cryptococcal screening is considered prior to ART initiation in patients with CD4 counts of less than 100 cells/mm 3 . When this recommendation is followed in our setup, many patients with cryptococcal antigenemia are likely to be missed.…”

“…Sometimes, ART can lead to an aberrant inflammatory response and paradoxical clinical worsening known as Immune Reconstitution Inflammatory Syndrome (IRIS). 3 This is due to subclinical opportunistic infections and disease exacerbations after starting ART. Therefore, screening for opportunistic infections is important in preventing IRIS.…”

Hemophagocytic syndrome in patients infected with the human immunodeficiency virus: A study of 15 consecutive patients

“…The three main situations that lead to this picture are septic hemophagocytic syndrome [8][9][10][11], shock [13] and immune reconstitution inflammatory syndrome [14]. Nevertheless, the boundaries between them are not always clear cut, and situations may arise in which various of the diagnostic criteria coexist [15][16][17].…”