Immune reconstitution inflammatory syndrome (IRIS)
After the initiation of ART in an HIV-infected individual, cellular immunity improves. There is an increase in CD4+ cells, CD4+/CD8+ ratio, and cytokines like interleukin-6 and interferon-γ, along with an imbalance in Th1/Th2 and the expression of CCR-3 and CCR-5 on monocytes and granulocytes. Consequently, some patients (up to 13%) develop a very profound inflammatory systemic response known as IRIS within 3–27 (mean = 9) months after starting ART. This syndrome is less likely to occur if the CD4+ count is >200–350/μL when ART is initiated, and the risk of IRIS is increased with lower CD4+ counts and higher viral loads. A patient with AIDS can be diagnosed with IRIS if they develop severe systemic inflammatory symptoms on ART associated with increasing CD4+ counts, decreasing HIV-1 viral load, and the symptoms cannot be explained by a new etiology or infection. The first phase of IRIS occurs within 8–12 weeks after initiation of ART and results from an increase in memory CD4+ cells. It can be associated with an exacerbation of preexisting RA, SLE, or sarcoidosis. The second phase occurs after 6 months of ART and results from naïve CD4+ cells and their cytokines. This can be associated with the onset of a new systemic or organ-specific autoimmune disease like RA, SLE, sarcoidosis, Still’s disease, PM, ReA, autoimmune thyroid disease, subacute cutaneous lupus or Guillain–Barre syndrome. In addition, opportunistic infections under treatment can worsen during this phase. IRIS tends to be a self-limited syndrome and generally ART is continued. If the inflammatory response is severe and threatens irreversible damage to the eyes or central nervous system, then ART may need to be discontinued and the patient treated with corticosteroids.
