IRIS – Immune Reconstitution Inflammatory Syndrome

Highly active antiretroviral therapy (HAART) has transformed the prognosis and the management of HIV-positive patients and led to a significant reduction in the prevalence of AIDS related symptoms. However, up to a quarter of patients starting or restarting HAART may experience exacerbation of opportunistic infections despite positive virological and immunological response to the therapy. This phenomenon is known as Immune Reconstitution Inflammatory Syndrome (IRIS). It involves a rapid and uncontrollable inflammatory reaction during the immune recovery process.

The paradox of clinical deterioration in the presence of a positive response to treatment has previously been documented in HIV-negative patients receiving TB treatment and in post transplantation patients. HIV-related IRIS is most likely to occur during treatment of advanced disease where there is a rapid fall in HIV RNA and dramatic reversal of the immmunosuppression. It usually presents within three months of commencing the anti-HIV treatment and is a result of an immune response against subclinical infection from viable microorganisms. Less commonly, HAART-related IRIS might be of late onset ( >3 months after commencing the treatment), as a response to target antigens of non-viable pathogens.

Evidence to date suggests that IRIS is triggered by the effective control of the HIV viremea. It progresses with the restoration of the pathogen-specific immunity combined with an inflammatory response. Consequently there is an exacerbation of undetected opportunistic infections, the recurrence of previously treated conditions or the development of neoplasms. Several conditions have been reported in the context of IRIS, including tuberculosis, pneumonia, cytomegalovirus infections and oral Kaposi’s sarcoma.

IRIS is a distinct yet diverse condition associated with high morbidity in HIV patients, in both high and low income countries. Until reliable biomarkers for accurate prediction and diagnosis of IRIS are discovered, clinicians must remain vigilant when managing patients at risk of developing this condition.