HIV
Conditions
Keywords
HIV, immunoactivation, bacterial translocation, prebiotics, glutamine, microbiota
Brief summary
A rapid and almost complete loss of CD4+ T cells from the gut associated lymphoid tissue (GALT) occurs early in HIV infection, with a permanent damage in the intestinal barrier, changes in gut microbiota, increased bacterial translocation and persistent immune activation, changes that are not restored after the initiation of antiretroviral therapy. The investigators hypothesize than an intervention targetting the enterocyte barrier and the gut microbiota might modify the gastrointestinal tract towards a bifidogenic microbiota and improve markers of bacterial translocation, inflammation, immune activation and endothelial dysfunction.
Detailed description
This is a randomized placebo-controlled clinical trial to evaluate the safety and effectiveness to modify gut microbiota, bacterial translocation, immune activation and markers of endothelial dysfunction of a dietary supplement (prebiotics + glutamine) during a period of six weeks. The study will enroll four cohorts: 1) HIV-infected, treatment naive individuals; 2) HIV-infected subjects, currently on ART, with \>350 CD4+ T-cells/uL; 3) HIV-infected subjects, currently on ART, with \<350 CD4+ T-cells/uL; 4) HIV negative healthy controls.
Interventions
DIETARY_SUPPLEMENTPrebiotics+Glutamine
Prebiotics are nondigestible food ingredients, generally oligosaccharides, that modify intestinal microbiota balance by stimulating the growth of beneficial bacteria. Glutamine is a non-essential amino acid that can be metabolized by epithelial cells, enhancing barrier function.
DIETARY_SUPPLEMENTPlacebo
Maltodextrin, 20 g.
Sponsors
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* After receiving information on the design and objectives of the study, the possible risks involved, and the fact that they can refuse to collaborate at any time, patients will give their informed consent to participate in the study and agree to provide material for the cellular and molecular studies. * Aged over 18 years. * Group 1: HIV+, Not receiving ART and no previous exposure to ART, at least 2 years since HIV diagnosis. * Group 2: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and more than 350 CD4+ T-cells/uL. * Group 3: HIV+, currently receiving ART for more than 2 years, HIV-1 RNA levels less than 40 copies/ml and less than 350 CD4+ T-cells/uL. * Group 4: HIV-, healthy controls.
Exclusion criteria
* Major cardiovascular risk factors. * Concomitant acute diseases. * Gastrointestinal disorders. * Pregnancy. * Antibiotic exposure in the previous month. * Regular use of foods or supplements containing prebiotics or probiotics within the 2 weeks prior to initiation of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in gut microbiota composition | 6 weeks | Changes in gut microbiota as determined by 454 pyrosequencing. |
| Changes in markers of bacterial translocation | 6 weeks | Soluble CD14 and increasing permeability binding protein. |
| Changes in markers of immunoactivation | 6 weeks | Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38. |
| Changes in inflammatory markers | 6 weeks | Changes in interleukine-6 and high-sensitivity C Reactive Protein |
| Changes in markers of endothelial dysfunction | 6 weeks | Changes in asymmetric dimethylarginine and flow-mediated dilation |
| Safety | 6 weeks | Adverse events monitoring during the intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gene expression in peripheral blood monocytic cells. | 6 weeks | — |
| Changes in gut microbiota | 6 weeks | Changes in gut microbiota by 454 pyrosequencing of fecal samples. |
| Disease progression in HIV-infected patients. | 6 weeks | Levels of CD4+ T-cell and HIV-1 RNA copies/mL |
| Thymic function | 6 weeks | — |
Countries
Spain
Outcome results
None listed