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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dietary Supplement: Prebiotics+Glutamine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prebiotics+Glutamine | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety | Adverse events monitoring during the intervention | 6 weeks |
| Changes in markers of bacterial translocation | Soluble CD14 and increasing permeability binding protein. | 6 weeks |
| Changes in markers of immunoactivation | Changes in percentages of CD4+ and CD8+ T-cells expressing CD25, HLADR, CD38. | 6 weeks |
| Changes in inflammatory markers | Changes in interleukine-6 and high-sensitivity C Reactive Protein | 6 weeks |
| Changes in markers of endothelial dysfunction | Changes in asymmetric dimethylarginine and flow-mediated dilation | 6 weeks |
| Changes in gut microbiota composition | Changes in gut microbiota as determined by 454 pyrosequencing. | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in gut microbiota | Changes in gut microbiota by 454 pyrosequencing of fecal samples. | 6 weeks |
| Disease progression in HIV-infected patients. | Levels of CD4+ T-cell and HIV-1 RNA copies/mL |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Ramón y Cajal and Hospital Clínico San Carlos | Madrid | 28034 | Spain |
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|
| Placebo | Dietary Supplement | Maltodextrin, 20 g. |
|
| 6 weeks |
| Thymic function | 6 weeks |
| Gene expression in peripheral blood monocytic cells. | 6 weeks |