title: Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation.
abstract: Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Claire
authors.initials: C
authors.lastname: Deleage
authors.affiliation: Clinical and Molecular Retrovirology Section/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.affiliation: SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Yuwadee
authors.initials: Y
authors.lastname: Phuang-Ngern
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Netanya G
authors.initials: NG
authors.lastname: Sandler
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Suchada
authors.initials: S
authors.lastname: Sukhumvittaya
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Surat
authors.initials: S
authors.lastname: Jongrakthaitae
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Siriwat
authors.initials: S
authors.lastname: Akapirat
authors.affiliation: SEARCH, Bangkok, Thailand.
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletscher
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand; SEARCH, Bangkok, Thailand.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kroon
authors.affiliation: Virus Isolation and Serology Laboratory Applied and Developmental Research Directorate Science Applications International Corporation, Frederick, Inc. National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, United States of America.
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Rapee
authors.initials: R
authors.lastname: Trichavaroj
authors.affiliation: SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nitiya
authors.initials: N
authors.lastname: Chomchey
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O Connell
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Viseth
authors.initials: V
authors.lastname: Ngauy
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: SEARCH, Bangkok, Thailand; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand; SEARCH, Bangkok, Thailand.
authors.forename: Mark S
authors.initials: MS
authors.lastname: de Souza
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America; SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D000208:Acute Disease; D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D012809:Colon, Sigmoid / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D058504:Th17 Cells / Q000473:pathology / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016207:Cytokines