Impact of early cART in the gut during acute HIV infection
Claire Deleage, … , Jacob D. Estes, on behalf of the RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups
Claire Deleage, … , Jacob D. Estes, on behalf of the RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups
Published July 7, 2016
Citation Information: JCI Insight. 2016;1(10):e87065. https://doi.org/10.1172/jci.insight.87065.
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Research Article AIDS/HIV

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 (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.

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

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Figure 6

Inflammation and immune activation within the gastrointestinal tract of acute HIV-infected and treated participants.

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Inflammation and immune activation within the gastrointestinal tract of ...
Ki-67+ cells were quantified in the lamina propria (LP) after 24 and 96 weeks of treatment in the Fiebig I/II (FI/II) group (week 0, n = 19; week 24, n = 14; week 96, n = 7) (A) and in the Fiebig III (FIII), IV/V group (week 0, n = 22; week 24, n = 13; week 96, n = 12) (B). TNF+ cells were quantified in the LP after 24 and 96 weeks of treatment in the FI/II group (week 0, n = 19; week 24, n = 14; week 96, n = 8) (C) and in the FIII, IV/V group (week 0, n = 22; week 24, n = 13; week 96, n = 9) (D). Sigmoid biopsies of FI/II (week 0, n = 19; week 24, n = 14; week 96, n = 6) (E) and FIII+ (week 0, n = 22; week 24, n = 13; week 96, n = 8) (F) participants were stained and quantified for MX dynamin like GTPase 1 (Mx1) before and 24 weeks and 96 weeks after initiation of combination antiretroviral therapy (cART). Indoleamine 2,3-dioxygenase+ (IDO-1) (G) and IL-17+ (H) cells were quantified in the LP of sigmoid biopsies in FI/II (week 0, n = 18; week 24, n = 12; week 96, n = 5) and FIII+ participants (week 0, n = 19; week 24, n = 10; week 96, n = 10) at the first visit (week 0) and followed over time at 24 weeks and 96 weeks after treatment. Each symbol represents a patient. FII is distinguishable from FI by the light-blue colored symbols, and FIV/V is distinguishable from FIII by the dark-blue colored symbols. Each point represents the median of a minimum of 3 quantified biopsies per participant. Following repeated-measures and linear mixed-effects (lme) analyses, post-hoc lme contrasts and pairwise nonparametric (Wilcoxon) tests were performed. Benjamini-Hochberg adjusted P values are reported.