title: Intestinal barrier dysfunction in HIV infection: pathophysiology, clinical implications and potential therapies.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
authors: Department of Internal Medicine, Division of Infectious Diseases, University Hospital of Patras, 26504, Patras, Greece, sassim@upatras.gr.
authors: S F
authors: SF
authors: Assimakopoulos
authors: D
authors: D
authors: Dimitropoulou
authors: M
authors: M
authors: Marangos
authors: C A
authors: CA
authors: Gogos
mesh_terms: D018988:Bacterial Translocation; D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007408:Intestinal Absorption; D007410:Intestinal Diseases / Q000382:microbiology / Q000503:physiopathology / Q000821:virology*; D007422:Intestines / Q000382:microbiology / Q000503:physiopathology* / Q000821:virology; D010539:Permeability