Immune restoration inflammatory syndrome (IRIS) is most likely to occur in individuals who start HAART with very advanced immune suppression, according to a Serbian study published in the March edition of HIV Medicine. The investigators, from the Institute of Infectious and Tropical Diseases in Belgrade also found that the risk of IRIS was extremely low for patients who achieved an increase in their CD4 cell count to above 400 cells/mm3.
Since the advent of HAART it has become clear that patients who commence anti-HIV therapy with severe immune suppression may be at risk of developing a recurrence of previous opportunistic infections. It is thought that this is due to the recovery of the immune system and the consequent inflammatory response to infections. Estimates of the prevalence of IRIS is individuals starting HAART vary considerably.
According, investigators conducted a retrospective analysis including the 389 individuals who started HAART at the HIV Department at Institute of Infectious and Tropical Diseases in Belgrade between 1998 and 2003. In total, 30% of patients were women and the median age was 41 years. Previous antiretroviral therapy using one or two drugs had been used by 55% of patients. Individuals continued to take prophylaxis against PCP pneumonia and toxoplasmosis until their CD4 cell count had had a sustained increase above 200 cells/mm3.
At the time of HAART initiation, 87% of individuals had an AIDS diagnosis, the mean CD4 cell count was 108 cells/mm3 and median viral load was a little under 40,000 copies/ml. 62% of patients had a CD4 cell count below 100 cells/mm3.
After a median of 35 months of HAART, mean CD4 cell count increased to 375 cells/mm3 and 77% of patients achieved a viral load below 50 copies/ml. The investigators note that 45% of patients experienced an increase in their CD4 cell count above 400 cells/mm3 as well as a fall in their viral load below 50 copies/ml.
In total 65 patients (17%) had at least one episode of IRIS. These included herpes zoster (shingles), which was the most common (26 patients). There were also four cases of pulomary tuberculosis, four of extra-pulmonary tuberculosis, three patients had CMV, three patients had crytococcosis and two patients had toxoplasmosis. In addition, three patients were detected with hepatitis B virus and 15 individuals with hepatitis C virus.
The cases of tuberculosis, toxoplasmosis, and crytococcosis occurred soon after the initiation of HAART before the individuals had stopped taking antimicrobial prophylaxis. None of the patients who developed herpes zoster had had this illness before. One patient with hepatitis C virus died of liver failure. In addition, one patient experience immune recovery vitritis, which did not resolve during two years of otherwise successful HAART.
There were no significant differences in median CD4 cell count increase and fall in viral load between patients who experienced IRIS and those who did not. Amongst patients who did experience IRIS mean CD4 cell count increased from a baseline of 108 cells/mm3 to 337 cells/mm3 and 80% achieved a viral load below 50 copies/ml.
Multivariate logistic regression analysis showed that the only significant risk factor of IRIS was a baseline CD4 cell count below 100 cells/mm3 (odds ratio 2.5). Further analysis showed that an increase in CD4 cell count above 400 cells/mm3 was protective against IRIS (odd ratio 0.3).
“We showed that the likelihood of developing [IRIS] was elevated for those who commenced HAART at an advanced stage of HIV disease, and conversely, extremely low in patients who achieved CD4 cell count rises above 400 cells/mm3”, write the investigators.
They conclude “any effort to decrease the incidence of [IRIS] should include HAART initiation before disease has reached an advanced stage [below 100 cells/mm3]. In patients with opportunistic infections as a consequence of HIV-induced immunodeficiency, it seems wise to complete antimicrobial therapy before commencing HAART.”
Jevtovic DJ et al. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med 6: 140 – 143, 2005.