Risk Factors for Immune Reconstitution Inflammatory Syndrome in Patients on HAART

Immune reconstitution inflammatory syndrome (IRIS), also known as immune restoration disease, occurs in some HIV patients after they start effective antiretroviral therapy as a consequence of immune recovery. IRIS can have many different manifestations related to flare-ups of pre-existing infections as the immune response becomes stronger. However, not all people starting HAART experience IRIS, and the risk factors are not fully understood.

As reported in the December 1, 2007 Journal of Acquired Immune Deficiency Syndromes, researchers at Johns Hopkins University in Baltimore sought to determine clinical risk factors for the development of IRIS.

Out of a cohort of about 200 patients at the Johns Hopkins HIV Clinic, 49 individuals who developed IRIS were identified and matched with 4 control subjects without IRIS who had started HAART at around the same time (within 6 months). The group as a whole had advanced immune suppression, with a median nadir (lowest-ever) CD4 count of 20 cells/mm³.

Results

• Patients presented with IRIS a median of 29 days after 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 (PI) (odds ratio [OR] 7.41; P = 0.006);
  
  
• Nadir CD4 count below 100 cells/mm³ (OR 6.2; P < 0.001);
  
  
• Plasma HIV RNA decrease of more than 2.5 log₁₀ from HAART initiation to occurrence of IRIS.
  
  
• Incrementally greater decreases in viral load directly correlated with increased risk for the development of IRIS.

Conclusion

In conclusion, the authors wrote, “The most immunosuppressed patients treated with the most potent regimens, particularly [boosted PI]-based regimens, resulting in significant HIV viral load declines are at greatest risk for the development of IRIS after HAART initiation.”