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Exploratory Study on the Role of the Digestive Microbiota in Adults Living With HIV-1

Withdrawn
Conditions
HIV
Interventions
Other: Stool sample collection
Other: Blood sample collection
Registration Number
NCT05724524
Lead Sponsor
Centre Hospitalier Universitaire de Nīmes
Brief Summary

Chronic immune activation present in aviremic people living with HIV under treatment promotes the onset of insulin resistance and metabolic syndrome, paving the way for the comorbidities that are currently the main causes of morbidity. This activation continues despite effective antiretroviral therapy. In the ACTIVIH study (NCT02334943) the analysis of 68 AI markers allowed classification of 120 aviremic PLHIV under treatment for at least 2 years according to 5 different immune activation profiles. Among these 5 profiles, Profile 2 was characterized by high blood pressure figures, high waist sizes, low HDL-cholesterol levels, high triglyceridemia, and especially hyperinsulinemia. Several studies have shown that the digestive microbiota of this population is less rich and less diverse than that of healthy subjects. However, the digestive microbiota and in particular bacterial proteins and metabolites seem to play a key role in immune activation in people living with HIV. Finally, the digestive microbiota has already been shown to have an impact on insulin sensitivity.

The study investigators hypothesize that a particular digestive microbiota could promote the appearance of Profile 2. This microbiota could be the cause of digestive dysbiosis leading to intestinal inflammation, digestive permeability and bacterial translocation.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Male
Target Recruitment
Not specified
Inclusion Criteria
  • Patient informed of the implementation of the study, its objectives, its constraints and the patient's rights.
  • Male and Caucasian patient.
  • Patient with HIV-1 infection determined by positive serology or plasma viral load (HIV RNA) measurement.
  • Patient on effective triple antiretroviral therapy, stable for more than 6 months, with a plasma viral load <50 copies / ml for at least 6 months before inclusion (2 measurements).
  • Patient whose immune activation profile has been characterized beforehand (profiles 1, 2, 3, 4 and 5).
  • The patient must have given their free and informed consent and signed the consent form
  • The patient must be a member or beneficiary of a health insurance plan
Exclusion Criteria
  • Vulnerable person according to article L1121-6 of the CSP.
  • Adult person protected according to article L1121-8 of the CSP.
  • Patient presenting with a non-infectious pathology which may be the cause of an immune abnormality.
  • Patient having undergone treatment with an immunomodulator molecule or chemotherapy within 60 days before inclusion in the research or has an indication planned for the duration of the research.
  • Patient with a chronic digestive pathology or who had been operated on the previous year
  • The subject is participating in a category 1 interventional study, has participated in another interventional study in the last 3 months or is in a period of exclusion determined by a previous study
  • The subject refuses to sign the consent
  • It is impossible to give the subject informed information
  • The patient is under safeguard of justice or state guardianship

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Other profilesBlood sample collectionPeople living with HIV with immune activation profiles1 + 3-5: T8, NK, T4 and monocyte profiles
Profile 2Stool sample collectionPeople living with HIV with immune activation profile 2: inflammatory profile - high level of sTNFRI
Profile 2Blood sample collectionPeople living with HIV with immune activation profile 2: inflammatory profile - high level of sTNFRI
Other profilesStool sample collectionPeople living with HIV with immune activation profiles1 + 3-5: T8, NK, T4 and monocyte profiles
Primary Outcome Measures
NameTimeMethod
Relative quantification of gut microbiota bacterial proteins in patients with immune activation profile 2 versus all other profilesDay 0

Percentage of the various bacterial proteins present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry (%)

Nature of gut microbiota bacterial proteins in patients with immune activation profile 2 versus all other profilesDay 0

Number of bacterial proteins present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry

Nature of gut microbiota taxonomy in patients with immune activation profile 2 versus all other profilesDay 0

Number of operational taxonomic units present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry

Relative quantification of gut microbiota taxonomy in patients with immune activation profile 2 versus all other profilesDay 0

Percentage of the various operational taxonomic units present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry (%)

Secondary Outcome Measures
NameTimeMethod
Richness of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profilesDay 0

Rarefaction curves

Level of phyla and minority species in the stool in patients with immune activation profile 2 versus all other profilesDay 0

high-performance liquid chromatography mass spectrometry

beta-diversity of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profilesDay 0

Unifrac

Level of CD14S in serum of patients with immune activation profile 2 versus all other profilesDay 0

ng/ml by ELISA

Level of Lipopolysaccharide Binding Protein (LBP) in serum of patients with immune activation profile 2 versus all other profilesDay 0

pg/ml by ELISA

Level of intestinal fatty acid binding protein (I-FABP) in serum of patients with immune activation profile 2 versus all other profilesDay 0

ng/ml by ELISA

Transcriptomic analysis of peripheral blood mononuclear cellsDay 0

RNAseq

Diversity of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profilesDay 0

Shannon index

Level of bacterial 16S rDNA in plasma of patients with immune activation profile 2 versus all other profilesDay 0

Copies/µl

Trial Locations

Locations (2)

CHU de Nîmes

🇫🇷

Nîmes, France

CHU Gui de Chauliac

🇫🇷

Montpellier, France

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