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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Profile 2 | People living with HIV with immune activation profile 2: inflammatory profile - high level of sTNFRI |
| |
| Other profiles | People living with HIV with immune activation profiles1 + 3-5: T8, NK, T4 and monocyte profiles |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stool sample collection | Other | 50mg stool sample taken for protein extraction |
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| Measure | Description | Time Frame |
|---|---|---|
| Nature of gut microbiota bacterial proteins in patients with immune activation profile 2 versus all other profiles | Number of bacterial proteins present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry | Day 0 |
| Nature of gut microbiota taxonomy in patients with immune activation profile 2 versus all other profiles | Number of operational taxonomic units present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry | Day 0 |
| Relative quantification of gut microbiota bacterial proteins in patients with immune activation profile 2 versus all other profiles | Percentage of the various bacterial proteins present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry (%) | Day 0 |
| Relative quantification of gut microbiota taxonomy in patients with immune activation profile 2 versus all other profiles | Percentage of the various operational taxonomic units present in stool samples from patients, identified by high-performance liquid chromatography mass spectrometry (%) | Day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Richness of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profiles | Rarefaction curves | Day 0 |
| Diversity of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profiles |
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Inclusion Criteria:
Exclusion Criteria:
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Adult men with HIV-1 infection on effective antiretroviral therapy stable for more than 6 months.
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Philippe Lavigne | Centre Hospitalier Universitaire de Nīmes | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Gui de Chauliac | Montpellier | France | ||||
| CHU de Nîmes |
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Plasma, serum and stool samples
| Blood sample collection | Other | Venous blood sample taken for analysis of serum and plasma |
|
Shannon index |
| Day 0 |
| beta-diversity of Firmicutes and Bacteroidetes in patients with immune activation profile 2 versus all other profiles | Unifrac | Day 0 |
| Level of phyla and minority species in the stool in patients with immune activation profile 2 versus all other profiles | high-performance liquid chromatography mass spectrometry | Day 0 |
| Level of CD14S in serum of patients with immune activation profile 2 versus all other profiles | ng/ml by ELISA | Day 0 |
| Level of Lipopolysaccharide Binding Protein (LBP) in serum of patients with immune activation profile 2 versus all other profiles | pg/ml by ELISA | Day 0 |
| Level of intestinal fatty acid binding protein (I-FABP) in serum of patients with immune activation profile 2 versus all other profiles | ng/ml by ELISA | Day 0 |
| Level of bacterial 16S rDNA in plasma of patients with immune activation profile 2 versus all other profiles | Copies/µl | Day 0 |
| Transcriptomic analysis of peripheral blood mononuclear cells | RNAseq | Day 0 |
| Nîmes |
| France |