18F-FDG-PET/CT value for early diagnosis of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV+ patients

545 Objectives HIV-1 infection usually results in depletion of CD4+ T cells with secondary increased vulnerability to opportunistic infections (OIs) and development of AIDS. Although current antiretroviral therapy (ART) regimens lead to restoration of CD4+ T cells and immune function, enabling individuals to mount an adequate immune response to pathogens and microbes, a subset of patients present paradoxical worsening of pre-existing infectious/inflammatory conditions, despite control of HIV viremia. This phenomenon is referred to as Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS generally occurs within the first 6 months after ART initiation. Early diagnosis of IRIS as well as identification of the subset of HIV+ patients with potential to develop IRIS is of utmost importance for the optimal management of these patients. Thus, we designed a prospective study to evaluate the potential clinical usefulness of 18F-FGD-PET/CT in IRIS diagnosis and characterization. Methods 17 ART-naive/HIV+ patients were prospectively evaluated with 18F-FDG-PET/CT scans before and one month after initiation of ART. Each scan was acquired 60 minutes after i.v. administration of approximately 10 mCi of 18F-FDG. In both studies of each patient (pre-ART, post-ART), volumes of interest (VOIs) were delineated in specific regions of interest including liver, spleen, bone marrow (L5 vertebra and right iliac bone), axillary and inguinal lymph nodes, as well as in hypermetabolic foci of non-physiologic 18F-FDG uptake (most likely infectious foci). Total glycolytic activity (TGA) for each VOI was obtained using MIM software. TGA values were compared at baseline, in correlation with the development of clinical IRIS. Results Eight out of the 18 patients were eventually classified as IRIS based on clinical presentation while 9 patients were deemed not to have developed IRIS. At baseline, patients who eventually developed IRIS syndrome had a higher burden of infectious lesions (p=0.007), and they showed significantly higher TGA in the bone marrow (p=0.018, Wilcoxon rank sum test) compared to non-IRIS patients. In response to ART, non-IRIS patients showed significant decrease in their bone marrow TGA (p=0.0039, Wilcoxon rank sum test) while those who developed IRIS showed a slight (non-significant) increase (Fig. 1). Furthermore, within the non-IRIS group, five out of 9 patients had a mixed response with almost half of the lesions showing increased uptake rather than decreased uptake after treatment. Conclusions Increased metabolic activity in the bone marrow before initiation of ART is associated with development of IRIS in HIV+ patients. In addition, 18F-FDG PET showed worsening of disease in patients who did not manifest clinical worsening, raising the possibility of subclinical IRIS, although the exact implications of this phenomenon as far as treatment remain unclear.