The immune reconstitution inflammatory syndrome related to HIV co-infections: a review

Abstract

The immune reconstitution inflammatory syndrome (IRIS) is a consequence of an excessive pathogen-specific immune recovery reaction and occurs in a subset of patients on antiretroviral therapy (ART). Infective forms of IRIS may present either as an 'unmasking' of a previously subclinical infection or the paradoxical clinical deterioration of an infection for which the patient received appropriate antimicrobial therapy. The most important risk factors for IRIS are a low CD4+ T-cell count and a short time between treatment of the infection and the commencement of ART. The general approach to the treatment of IRIS is to continue ART and provide antimicrobial therapy for the provoking infection. The majority of cases are self-limiting; however, mortality and hospitalisation rates are particularly high when tuberculosis- or cryptococcal-IRIS affects the central nervous system (CNS). Corticosteroid therapy should be considered in certain forms of IRIS after the exclusion of other conditions that could explain the inflammatory manifestations in the patients. Given that a low CD4+ T-cell count is a major risk factor for the development of IRIS, commencing ART at a CD4+ T-cell count of >350/μL will prevent most cases.

Immune Reconstitution Inflammatory Syndrome

“…7 Corticosteroids, the only agents that have been proven to be effective by clinical trials (for treating paradoxical tuberculosis-associated IRIS), are the most frequently used therapeutic agents for IRIS. Limited information is available about the efficacy of other agents, including the non-steroidal anti-inflammatory drugs pentoxifylline, montelukast, thalidomide, and hydroxychloroquine.…”

Visceral Leishmaniasis Relapse in HIV Patients—A Role for Myeloid-Derived Suppressor Cells?

“…Comorbidities of HIV and other infectious diseases such as tuberculosis, cryptococcosis, or viral hepatitis manifest a number of general characteristics including accelerated disease progression, higher rates of adverse outcomes, and therapy-associated complications like the immune reconstitution inflammatory syndrome (IRIS) [2]. While HIV-VL coinfection is also associated with accelerated HIV and VL progression and a poor prognosis, it appears to be governed by a number of unique and poorly explained features.…”

“…In other patients, the unique entity of “active chronic visceral leishmaniasis” was described, entailing continuous asymptomatic parasite replication under therapy, interspersed with symptomatic secondary VL episodes [4]. The observed therapeutic failure contrasts sharply with, e.g., the IRIS events observed in other coinfections, which—while detrimental—are indicative of a partial and possibly even over-exuberant restoration of pathogen-specific immune responses [2]. This therapeutic failure in HIV-VL poses a major challenge to programmes facing a high burden of the coinfection—however, it remains poorly understood and under-researched.…”

Commentary

“…It has been attributed to a sudden, inappropriate, treatment-induced surge in immunity causing an intense reaction to the infective pathogen, and resulting in the immune reconstitution inflammatory syndrome (IRIS). [4] Occurring in 10-25% of patients,[1] IRIS is usually self-limiting; however, fatal reactions have been described, particularly when the reaction involves the central nervous or respiratory systems. [45]…”

“…[4] Occurring in 10-25% of patients,[1] IRIS is usually self-limiting; however, fatal reactions have been described, particularly when the reaction involves the central nervous or respiratory systems. [45]…”