Immune Reconstitution Inflammatory Syndrome: Risk Factors and Treatment Implications

Background: Immune reconstitution inflammatory syndrome (IRIS), also called immune restoration disease, occurs in a subset of HIV-infected patients after the initiation of highly active antiretroviral therapy (HAART) and can be diagnostically challenging and difficult to treat. We sought to determine clinical risk factors for the development of IRIS.

Methods: Patients from the Johns Hopkins HIV Clinic who had IRIS were identified and matched with 4 controls without IRIS who had initiated HAART within 6 months of the case.

Results: Forty-nine cases of IRIS were identified; patients presented a median of 29 days from the initiation of HAART (range: 4 to 186 days). A multivariate analysis showed that the development of IRIS was independently associated with using a boosted protease inhibitor (BPI) (odds ratio [OR] = 7.41; P = 0.006), a nadir CD4 count <100 cells/mm(3) (OR = 6.2; P < 0.001), and a plasma HIV viral RNA decrease of more than 2.5 log at the time of IRIS compared with RNA levels before the initiation of HAART. Incrementally greater decreases in viral loads directly correlated with increased risk for the development of IRIS.

Conclusions: The most immunosuppressed patients treated with the most potent regimens, particularly BPI-based regimens, resulting in significant HIV viral load declines are at greatest risk for the development of IRIS after HAART initiation.