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Infection

, Volume 42, Issue 6, pp 951–959 | Cite as

Intestinal barrier dysfunction in HIV infection: pathophysiology, clinical implications and potential therapies

  • S. F. Assimakopoulos
  • D. Dimitropoulou
  • M. Marangos
  • C. A. Gogos
Review

Abstract

Introduction

Current pathogenetic aspects on HIV infection highlight the importance of a chronic immune activation ultimately leading to T lymphocyte homeostasis disruption and immune deregulation associated with disease manifestations and progression. It is widely accepted that this continuous immune activation in HIV infection is principally driven by the phenomenon of pathological microbial translocation (MT).

Methods

Review of the literature on the role of intestinal barrier dysfunction in HIV infection, with emphasis on the implicated pathophysiological mechanisms, clinical implications and potentially effective therapeutic interventions.

Findings

MT in HIV infection is promoted by a multifactorial disruption of all major levels comprising the intestinal barrier defense. Specifically, HIV infection disrupts the integrity of the intestinal biological (quantitative and qualitative alterations of gut microecology, overgrowth of pathogenic bacteria), immune (depletion of CD4(+) T cells, especially Th17 cells, increased CD4+ FoxP3+ Tregs, decreased mucosal macrophages phagocytic capacity, development of intestinal proinflammatory milieu) and mechanical barrier (enterocytes’ apoptosis, disruption of tight junctions). Intestinal barrier dysfunction allows the passage of microbes and immunostimulatory bioproducts from the gut lumen first in the lamina propria and thereafter in the systemic circulation, thus continuously promoting a local and systemic inflammatory response. This chronic immune activation is associated with HIV disease progression, suboptimal response to HAART and development of non-AIDS comorbidities.

Conclusions

We have reached a point where the effective control of HIV viremia by HAART should be combined with emerging pharmacological approaches aiming at the restoration of the intestinal barrier, targeting its diverse levels of structure and function. Elimination of the MT phenomenon would mitigate its effect on immune homeostasis, which might improve the prognosis of the HIV-infected patient in terms of morbidity and mortality.

Keywords

HIV AIDS Intestinal barrier Intestinal permeability Microbial translocation Bacterial translocation Endotoxemia 

Notes

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • S. F. Assimakopoulos
    • 1
  • D. Dimitropoulou
    • 1
  • M. Marangos
    • 1
  • C. A. Gogos
    • 1
  1. 1.Department of Internal Medicine, Division of Infectious DiseasesUniversity Hospital of PatrasPatrasGreece

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