Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis

Xiaorong Peng; Stéphane Isnard; John Lin; Brandon Fombuena; Talat Bessissow; Nicolas Chomont; Jean-Pierre Routy

doi:10.1016/j.jve.2021.100033

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis

J Virus Erad. 2021 Feb 15;7(1):100033. doi: 10.1016/j.jve.2021.100033. eCollection 2021 Mar.

Authors

Xiaorong Peng^{1

2

3}, Stéphane Isnard^{1

2

4}, John Lin^{1

2}, Brandon Fombuena^{1

2}, Talat Bessissow⁵, Nicolas Chomont⁶, Jean-Pierre Routy^{1

2

7}

Affiliations

¹ Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC, Canada.
² Chronic Viral Illness Service, McGill University Health Centre, Montréal, QC, Canada.
³ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
⁴ CIHR Canadian HIV Trials Network, Vancouver, BC, Canada.
⁵ Division of Gastroenterology, McGill University Health Center, Montréal, QC, Canada.
⁶ Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
⁷ Division of Hematology, McGill University Health Centre, Montréal, QC, Canada.

Abstract

The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold higher frequency of cells harboring HIV DNA in inflamed compared to non-inflamed colon tissue. Analysis of the expression of occludin-1 and claudin-3 confirmed our macroscopic characterization of inflamed and non-inflamed colon. Our results confirm that increased gut permeability and inflammation are associated with a higher frequency of infected cells and suggest that restoring gut barrier integrity may be used as a strategy to reduce inflammation and HIV persistence in the gut.

Keywords: Colon; Gut barrier integrity; HIV DNA; Inflammation; Reservoir; Ulcerative colitis.