Impact of early cART in the gut during acute HIV infection

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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Article numbere87065
JournalJCI Insight
Volume1
Issue number10
DOIs
StatePublished - Jul 7 2016

Bibliographical note

Funding Information:
We thank our study participants and staff from the Thai Red Cross AIDS Research Centre and the Silom Community Clinic in Bangkok for their valuable contributions to this study. SEARCH is a research collaboration between the Thai Red Cross AIDS Research Centre (TRCARC), the University of Hawaii, UCSF, and the Department of Retrovirology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences (Yuwadee Phuang-Ngren, Chayada Sajjawerawan, Rapee Trichavaroj, Robert O?Con-nell, Nantana Tantibul, Siriwat Akapirat, Surat Jongrakthaitae). The empirical component of this study was funded by the US Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, USA, under a cooperative agreement (W81XWH-07-2-0067) with the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. at the US Department of Defense. The scientific component of this study was funded in part with federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E, and the Delaney AIDS Research Enterprise (U19AI096109). The work of I. Sereti was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/NIH. We also thank the UCLA Center for AIDS Research (CFAR) Mucosal Immunology Core Laboratory, funded by UCLA CFAR grant 5P30 AI028697, for their support and guidance regarding the isolation of mucosal mast cells. We thank the members of the Pathology Histology Laboratory of Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., for their service. The RV254/SEARCH 010 and RV304/SEARCH 013 study groups include Praphan Phanuphak, Nipat Teeratakulpisarn, Eugene Kroon, Donn Colby, Duanghathai Suttichom, Somprartthana Rattanama-nee, Peeriya Prueksakaew, Somporn Tipsuk, Putthachard Karnsomlap, Sasiwimol Ubolyam, and Pacha-rin Eamyoung from SEARCH/TRCARC/HIV-NAT. See Supplemental Acknowledgments for consortia details (supplemental material available online with this article; doi:10.1172/jci.insight.87065DS1). The content of this publication does not necessarily reflect the views or policies of the US Army, the National Cancer Institute, the US Department of Defense, the Department of Health and Human Services, and the US Centers for Disease Control and Prevention nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Funding Information:
We thank our study participants and staff from the Thai Red Cross AIDS Research Centre and the Silom Community Clinic in Bangkok for their valuable contributions to this study. SEARCH is a research collaboration between the Thai Red Cross AIDS Research Centre (TRCARC), the University of Hawaii, UCSF, and the Department of Retrovirology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences (Yuwadee Phuang-Ngren, Chayada Sajjawerawan, Rapee Trichavaroj, Robert O’Con-nell, Nantana Tantibul, Siriwat Akapirat, Surat Jongrakthaitae). The empirical component of this study was funded by the US Military HIV Research Program, Walter Reed Army Institute of Research, Rock-ville, Maryland, USA, under a cooperative agreement (W81XWH-07-2-0067) with the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. at the US Department of Defense. The scientific component of this study was funded in part with federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E, and the Delaney AIDS Research Enterprise (U19AI096109). The work of I. Sereti was supported by the intramural research program of National Institute of Allergy and Infectious Diseases/NIH. We also thank the UCLA Center for AIDS Research (CFAR) Mucosal Immunology Core Laboratory, funded by UCLA CFAR grant 5P30 AI028697, for their support and guidance regarding the isolation of mucosal mast cells. We thank the members of the Pathology Histology Laboratory of Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., for their service. The RV254/SEARCH 010 and RV304/SEARCH 013 study groups include Praphan Phanuphak, Nipat Teeratakulpisarn, Eugene Kroon, Donn Colby, Duanghathai Suttichom, Somprartthana Rattanama-nee, Peeriya Prueksakaew, Somporn Tipsuk, Putthachard Karnsomlap, Sasiwimol Ubolyam, and Pacha-rin Eamyoung from SEARCH/TRCARC/HIV-NAT. See Supplemental Acknowledgments for consortia details (supplemental material available online with this article; doi:10.1172/jci.insight.87065DS1). The content of this publication does not necessarily reflect the views or policies of the US Army, the National Cancer Institute, the US Department of Defense, the Department of Health and Human Services, and the US Centers for Disease Control and Prevention nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Publisher Copyright:
© 2019 American Society for Clinical Investigation. All rights reserved.

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