Gut-Associated Lymphocyte Trafficking

Study Overview
=================
Brief Summary
-----------------
The gut immune barrier is not fully restored in HIV-1-infected subjects despite they were receiving antiretroviral treatment. This leaky gut leads to microbial translocation from the gut lumen into the bloodstream that fuels deleterious systemic inflammation. The chemotaxis axes that allow T lymphocytes to migrate from the blood to the gut mucosa in order to reconstitute the mucosal immune barrier seems altered in treated HIV-1-infected subjects.This study aims at better understanding the mechanisms involved in this lack of mucosal immune restoration.

Detailed Description
-----------------
Pathophysiological study in human subjects, comparative, national, multicentric and prospective. Peripheral blood and intestinal biopsies will be collected.

Official Title
-----------------
Altered Homing of T Lymphocytes to the Gut and Poor Immune Reconstitution of the Intestinal Mucosa in Treated HIV-infected Individuals

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Other: Peripheral blood and intestinal biopsies will be collected


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria are: For HIV-1-infected subjects group : Age at least 18-year old HIV-1 infection Receiving continuous cART for ≥ 12 months, started during the chronic phase Plasma viral load ≤50 copies/mL for ≥ 6 months (one blip ≤200 copies/mL authorized) Blood CD4+ T cells count ≥ 350 cells/mm3 Indication for upper and/or lower digestive endoscopy Patient enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme) Written informed consent. For uninfected control group : Age at least 18-year old Indication for upper and/or lower digestive endoscopy Patient enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme) Written informed consent Exclusion Criteria are: For HIV-1-infected subject group : HIV-2 infection Inflammatory bowel diseases (Crohn's disease, ulcerative colitis) ; coeliac disease Platelets count <50 G/L or abnormal hemostasis tests Decompensated cirrhosis Past or current lymphoma Involvement in an HIV-1 immunotherapeutic vaccine study Pregnant or breastfeeding women Subjects participating in a study excluding participating in another study Vulnerability, such as an age under 18, tutorship, trusteeship, or subjects deprived of liberty by a legal or administrative decision. For uninfected control group : HIV-1 and 2 infection Inflammatory bowel diseases (Crohn's disease, ulcerative colitis) ; coeliac disease Platelets count <50 G/L or abnormal hemostasis tests Decompensated cirrhosis Past or current lymphoma Pregnant or breastfeeding women Subjects participating in a study excluding participating in another study Vulnerability, such as an age under 18, tutorship, trusteeship, or subjects deprived of liberty by a legal or administrative decision

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV-1 infected subjects<br>40 subjects will be recruited in the Department of Infectious Diseases of Toulouse University Hospital, France: 15 subjects will have an upper endoscopy (gastroscopy) with duodenal sampling 15 subjects will have a lower endoscopy (coloscopy) with colonic and ileal sampling 10 subjects will have both a gastroscopy and a coloscopy | Other: Peripheral blood and intestinal biopsies will be collected<br>* Blood draw and intestinal biopsies<br>|
| Other: Uninfected-controls<br>40 subjects will be recruited in the Department of Internal Medicine of Toulouse University Hospital, France: 10 subjects will have an upper endoscopy (gastroscopy) with duodenal sampling 10 subjects will have a lower endoscopy (coloscopy) with colonic and ileal sampling 20 subjects will have both a gastroscopy and a coloscopy | Other: Peripheral blood and intestinal biopsies will be collected<br>* Blood draw and intestinal biopsies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune status: Measure of the frequencies of Th1 in peripheral blood and gut mucosa. | The frequencies of Th1 will be measured by flow cytometry. | Baseline | 
| Immune status: Measure of the frequencies of Th17 in peripheral blood and gut mucosa. | The frequencies of Th17 will be measured by flow cytometry. | Baseline | 
| Immune status: Measure of the frequencies of Th22 in peripheral blood and gut mucosa. | The frequencies of Th22 will be measured by flow cytometry. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune status: Quantification of cytokines in blood and gut mucosa. | The quantification of cytokines will be measured by luminex. | Baseline | 
| Immune status: Quantification of cytokines in blood and gut mucosa. | The quantification of cytokines will be measured by immuno-histochemistry. | Baseline | 
| Immune status: Quantification of chemiokines in blood and gut mucosa. | The quantification of chemiokines will be measured by luminex. | Baseline | 
| Immune status: Quantification of chemiokines in blood and gut mucosa. | The quantification of chemiokines will be measured by immuno-histochemistry. | Baseline | 
| Microbial translocation : Quantification of soluble CD14 in plasma. | The quantification of CD 14 will be realised by Enzyme-Linked Immunosorbent Assay (ELISA). | Baseline | 
| Microbial translocation : Quantification of soluble soluble CD163 in plasma. | The quantification of CD163 will be realised by Enzyme-Linked Immunosorbent Assay (ELISA) . | Baseline | 
| Microbial translocation : Quantification of Lipopolysaccharide Binding Protein (LBP). | The quantification of Lipopolysaccharide Binding Protein will be realised by Enzyme-Linked Immunosorbent Assay (ELISA). | Baseline | 
| Microbial translocation : Quantification of Intestinal-type Fatty Acid-Binding Protein (I-FABP) in plasma. | The quantification of Intestinal-type Fatty Acid-Binding Protein (I-FABP) will be realised by Enzyme-Linked Immunosorbent Assay (ELISA). | Baseline | 
| Microbial translocation : Quantification of 16S RNA. | The quantification of 16S RNA will be realised by real-time Polymerase Chaine Reaction (qPCR). | Baseline |