Primary HIV infection features colonic damage and neutrophil inflammation yet containment of microbial translocation

Abstract

Introduction: Impairment of the gastrointestinal (GI) barrier leads to microbial translocation and peripheral immune activation which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely- and chronically-infected, combination cART-naïve individuals. Methods: Fifteen people with Primary HIV infection (P-HIV) and 13 with Chronic HIV infection (C-HIV) c-ART naïve participants were cross-sectionally studied. Gut biopsies were analyzed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3+panγδ+Vδ1+/Vδ2+). In plasma we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA). Results: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared to C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV. Conclusions: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely due to a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.