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 Estes

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 2019

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HIV Infections
Gastrointestinal Tract
HIV
Inflammation
T-Lymphocytes
Mucous Membrane
Biopsy
Therapeutics
Colon
Immunohistochemistry
Infection
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Deleage, C., Schuetz, A., Alvord, W. G., Johnston, L., Hao, X. P., Morcock, D. R., ... Estes, J. (2019). Impact of early cART in the gut during acute HIV infection. JCI Insight, 1(10), [e87065]. https://doi.org/10.1172/jci.insight.87065

Impact of early cART in the gut during acute HIV infection. / Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Sereti, Irini; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat; Estes, Jacob.

In: JCI Insight, Vol. 1, No. 10, e87065, 07.07.2019.

Research output: Contribution to journalArticle

Deleage, C, Schuetz, A, Alvord, WG, Johnston, L, Hao, XP, Morcock, DR, Rerknimitr, R, Fletcher, JLK, Puttamaswin, S, Phanuphak, N, Dewar, R, McCune, JM, Sereti, I, Robb, M, Kim, JH, Schacker, TW, Hunt, P, Lifson, JD, Ananworanich, J & Estes, J 2019, 'Impact of early cART in the gut during acute HIV infection', JCI Insight, vol. 1, no. 10, e87065. https://doi.org/10.1172/jci.insight.87065
Deleage C, Schuetz A, Alvord WG, Johnston L, Hao XP, Morcock DR et al. Impact of early cART in the gut during acute HIV infection. JCI Insight. 2019 Jul 7;1(10). e87065. https://doi.org/10.1172/jci.insight.87065
Deleage, Claire ; Schuetz, Alexandra ; Alvord, W. Gregory ; Johnston, Leslie ; Hao, Xing Pei ; Morcock, David R. ; Rerknimitr, Rungsun ; Fletcher, James L.K. ; Puttamaswin, Suwanna ; Phanuphak, Nittaya ; Dewar, Robin ; McCune, Joseph M. ; Sereti, Irini ; Robb, Merlin ; Kim, Jerome H. ; Schacker, Timothy W. ; Hunt, Peter ; Lifson, Jeffrey D. ; Ananworanich, Jintanat ; Estes, Jacob. / Impact of early cART in the gut during acute HIV infection. In: JCI Insight. 2019 ; Vol. 1, No. 10.
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