Virology

Biography

Biography: Lucero Ramon-Luing

Abstract

Immune reconstitution inflammatory syndrome (IRIS) refers to the paradoxical deterioration or unmasking of infections after antiretroviral therapy (ART). Although a high proportion of IRIS events are secondary to M. tuberculosis infection, a variety of other opportunistic infections have also been implicated. Our goal is to study highly specific molecules related to infection and systemic inflammation and to elucidate their potential predictive and diagnostic value as IRIS biomarkers. This is a prospective cohort study, currently, forty-eight HIV+ patients naïve to treatment have been enrolled. We evaluated markers of T cell activation (HLA DR, CD38 and Glut-1) and exhaustion (Tim-3 and PD-1) on CD4+ and CD8+ T cells, CD4 count and plasma viral load at baseline (pre-ART), 8 weeks after ART and around the IRIS events. Gene expression of Tim-3, Galectin-9, Glut-1, CXCL10 and Granulysin was analyzed by qPCR. Among the 48 HIV+ patients, 13 developed herpes associated-IRIS. At baseline HIV+ patients who lately developed IRIS showed an increased expression of Tim-3, PD-1 and Glut-1 receptors on T cells compared with those IRIS- (P=0.001). A highly activated phenotype (CD38, Glut-1, HLA-DR, Tim-3 and PD-1 expression) was also identified in HIV+IRIS+ patients. Early ART initiation resulted in a decline in CD38, PD-1, and Tim-3 expression on HIV+IRIS- patients at the 8 weeks (P=0.01). Tim-3 and Glut-1 mRNA relative expression levels were elevated after 8 weeks of ART and significantly more elevated during the IRIS events. Relative mRNA level of CXCL10, was reduced in HIV+IRIS- patients. Granulysin relative expression did not have significant changes among patients. Our data suggest that longitudinal measurements of T cell activation and exhaustion markers should be included alongside HIV-1 mRNA levels. This type of analysis is important for understanding the immune mechanisms underlying IRIS development, which must be explored in larger cohorts.