Clinical trial NCT02906137: Gut-Associated Lymphocyte Trafficking
Official title: Altered Homing of T Lymphocytes to the Gut and Poor Immune Reconstitution of the Intestinal Mucosa in Treated HIV-infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1 Infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2016-09-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Immune status: Measure of the frequencies of Th1 in peripheral blood and gut mucosa.
timeFrame: Baseline
measure: Immune status: Measure of the frequencies of Th17 in peripheral blood and gut mucosa.
timeFrame: Baseline
measure: Immune status: Measure of the frequencies of Th22 in peripheral blood and gut mucosa.
timeFrame: Baseline
Secondary outcomes:
measure: Immune status: Quantification of cytokines in blood and gut mucosa.
timeFrame: Baseline
measure: Immune status: Quantification of cytokines in blood and gut mucosa.
timeFrame: Baseline
measure: Immune status: Quantification of chemiokines in blood and gut mucosa.
timeFrame: Baseline
measure: Immune status: Quantification of chemiokines in blood and gut mucosa.
timeFrame: Baseline
measure: Microbial translocation : Quantification of soluble CD14 in plasma.
timeFrame: Baseline
measure: Microbial translocation : Quantification of soluble soluble CD163 in plasma.
timeFrame: Baseline
measure: Microbial translocation : Quantification of Lipopolysaccharide Binding Protein (LBP).
timeFrame: Baseline
measure: Microbial translocation : Quantification of Intestinal-type Fatty Acid-Binding Protein (I-FABP) in plasma.
timeFrame: Baseline
measure: Microbial translocation : Quantification of 16S RNA.
timeFrame: Baseline
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Hôpital Purpan - Service de Médecine Interne
city: Toulouse
country: France
facility: Hôpital Purpan - Service des maladies Infectieuses
Study officials:
References: