Inflammation

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Despite dramatic advances in the successful treatment of HIV infection with combined antiretroviral therapy (cART), non-AIDS morbidity and mortality nevertheless remain higher in treated HIV-infected people compared to those who are not infected. Heightened systemic T cell activation is associated with poor CD4 T cell reconstitution, which in turn predicts poor long-term clinical outcome. Furthermore, raised circulating markers of inflammation, particularly IL-6 and D-dimers, are highly significant predictors of long-term morbidity and mortality during cART independently of plasma virus load and CD4 T cell count. In this project we studied the causes and consequences of inflammation in humans with a particular interest in the effects of microbial translocation from the gut. We recruited a cohort of 11 research participants at the Joint Clinical Research Center (JCRC) in Kampala Uganda. Participants were required to be HIV+ with detectable plasma HIV viremia and have no history of prior antiretroviral therapy (ART) use. Individuals were randomized to receive different cART drug regimens. We aimed at understanding how the extent and nature of microbial translocation at the species level changes over time after cART initiation and how these changes differentially affect CD4 T cell recovery and systemic inflammation, two paramount outcome measures of treated HIV disease. We measured inflammatory markers, immune cell transcriptomes, microbial species and metabolic markers. We found that the translocation of different microbial species shapes the inflammatory and metabolic profile of the host.