Year: 2016
Type: article
Abstract: Early after HIV infection there is substantial depletion of CD4 + T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (Mx1, TNF-α), immune activation (Ki-67), and the CD4 + T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4 + T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4 + T cells after 96 weeks of cART.
Source: JCI Insight
Authors: Claire Deleage, Alexandra Schuetz, W. Gregory Alvord, Leslie Johnston, Xing-Pei Hao, David R. Morcock, Rungsun Rerknimitr, James L.K. Fletcher, Suwanna Puttamaswin, Nittaya Phanuphak, Robin Dewar, Joseph M. McCune, Irini Sereti, Merlin Robb, Jerome H. Kim, Timothy W. Schacker, Peter Hunt, Jeffrey D. Lifson, Jintanat Ananworanich, Jacob D. Estes, on behalf of the RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups
Institutions: Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Henry M. Jackson Foundation, Armed Forces Research Institute of Medical Science, Data Management Services (United States), Chulalongkorn University, Thai Red Cross Society, National Cancer Institute, Science Applications International Corporation (United States), University of California, San Francisco, National Institutes of Health, National Institute of Allergy and Infectious Diseases, International Vaccine Institute, University of Minnesota
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Henry M. Jackson Foundation, Delaney AIDS Research Enterprise, Frederick National Laboratory for Cancer Research, Leidos, National Institutes of Health, Centers for Disease Control and Prevention, Center for AIDS Research, University of Washington, University of California, San Francisco, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Center for AIDS Research, University of California Los Angeles
Awards: G1345503394, G1546679804, G1589278233, G1685810784, DARE: Delaney AIDS Research Enterprise to find a cure., G3503792436, G386607036, G4119534169, G4382062407, G4585269469, G4713330150, G4988656331, G5146053897, G5850682332, G5867949827, G5888954722, G6112660351, G6812101401, UCLA Center for AIDS Research (CFAR), US MILITARY HUMAN IMMONODEFIECIENCY VIRUS (HIV) RESEARCH PROGRAM, G9000014846, G97119092
OpenAlex ID: W2471154607