title: Impact of early cART in the gut during acute HIV infection.
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 (M×1, 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.
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Deleage
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. ; US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: Statistical Consulting, Data Management Services Inc., Frederick, Maryland, USA.
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Alvord
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Johnston
authors.affiliation: Pathology and Histotechnology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: Xing-Pei
authors.initials: XP
authors.lastname: Hao
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Morcock
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.affiliation: SEARCH, Bangkok, Thailand. ; Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: SEARCH, Bangkok, Thailand. ; Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Suwanna
authors.initials: S
authors.lastname: Puttamaswin
authors.affiliation: SEARCH, Bangkok, Thailand. ; Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: Virus Isolation and Serology Laboratory, Applied and Developmental Research Directorate, Science Applications International Corp., Frederick Inc. National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.affiliation: Division of Experimental Medicine, Department of Medicine, UCSF, San Francisco, California, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Merlin
authors.initials: M
authors.lastname: Robb
authors.affiliation: US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA. ; SEARCH, Bangkok, Thailand. ; International Vaccine Institute, Seoul, South Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.affiliation: Positive Health Program, Department of Medicine, UCSF, San Francisco, California, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hunt
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA. ; SEARCH, Bangkok, Thailand.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes