Microbial translocation is correlated with HIV evolution in HIV-HCV co-infected patients.

Jean-Jacques Tudesq,Christophe Combescure,Albert Sotto,Catherine Dunyach-Remy,Jean-Philippe Lavigne,Régine Doncesco,Didier Laureillard

doi:10.1371/journal.pone.0183372

Abstract

Microbial translocation (MT) is characterized by bacterial products passing into the blood through the gut barrier and is a key phenomenon in the pathophysiology of Human Immunodeficiency Virus (HIV) infection. MT is also associated with liver damage in Hepatitis C Virus (HCV) patients. The aim of the study was to assess MT in plasma of HIV-HCV co-infected patients. 16S rDNA (16 S Ribosomal DNA subunit) marker and other markers of MT such as Lipopolysaccharide (LPS)-binding protein (LBP), soluble CD14 (sCD14), intestinal fatty acid binding protein (I-FABP) were used. Clinical, biological and immunological characteristics of the population were studied in order to correlate them with the intensity of the MT. We demonstrate that indirect markers of MT, LBP and CD14s, and a marker of intestinal permeability (I-FABP) are significantly higher in HIV-HCV co-infected patients than in healthy controls (17.0 vs 2.6 μg/mL, p < 0.001; 1901.7 vs 1255.0 ng/mL, p = 0.018); 478.3 vs 248.1 pg/mL, p < 0.001, respectively), while a direct marker of MT (16S rDNA copies) is not different between these two populations. However, plasma 16S rDNA was significantly higher in co-infected patients with long-standing HIV infections (RGM = 1.47 per 10 years, CI95% = [1.04:2.06], p = 0.03). Our findings show that in HIV-HCV co-infected patients, plasma 16S rDNA levels, directly reflecting MT, seem to be linked to the duration of HIV infection, while elevated levels of LBP and sCD14 reflect only a persistence of immune activation. The levels of these markers were not correlated with HCV evolution.

Highlights

Microbial translocation (MT) is a feature in people living with HIV, and is associated with immune activation, a negative prognosis factor in HIV infection [1,2,3,4,5,6,7,8]
Half of the patients (56.3%) were infected with hepatitis C virus (HCV)-1 genotype and a quarter (25.0%) with HCV-3, which is associated with a better prognosis [16]
Indirect markers of MT (LBP, sCD14S) were significantly higher in co-infected patients than in healthy controls, reflecting a persistence of immune activation correlated with the HIV evolution in these patients

Summary

Introduction

Microbial translocation (MT) is a feature in people living with HIV, and is associated with immune activation, a negative prognosis factor in HIV infection [1,2,3,4,5,6,7,8]. Assessment of microbial translocation in HIV-HCV co-infected patients infected efficient anti-retroviral therapy (ART) in HIV mono-infected patients leads to a reduction of MT, immune activation persists [5,7]. This persistent innate and acquired immune activation contributes to the pathogenesis of non-AIDS-related diseases [2]. In HIV-HCV co-infected patients, this immune activation promotes HCV hepatic fibrosis progression, resulting in poorer prognosis compared to HIV mono-infected patients, even in ART-controlled HIV [10,11,12]

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