HIV
Conditions
Keywords
HIV, Lactobacillus casei Shirota, NK cell, CD4, Lymphocyte, Cell activation, Antiretroviral therapy, Immune discordants
Brief summary
In this study, HIV-infected patients with poor recovery of CD4+ T cells and successful viral control after treatment with antiretroviral therapy will be enrolled to receive once a day Lactobcillus casei Shirota or placebo in a double-blind, randomized fashion. Immune parameters will be monitored for 12 weeks in both arms. The main outcome is CD4+ T cell recovery. Secondary outcomes will include NK cells and T cells immune parameters.
Detailed description
In this study, HIV-infected patients with poor recovery of CD4+ T cells and successful viral control after treatment with antiretroviral therapy will be enrolled to receive once a day Lactobcillus casei Shirota or placebo in a double-blind, randomized fashion. The main objective is to investigate whether the continuous, once a day, 12-weeks use of Yakult product containing Lactobacillus casei Shirota could affect immunological parameters in HIV-infected patients on suppressive antiretroviral treatment with poor CD4+ T cell recovery. A total of 48 volunteers will be followed for 12 week after initiation of daily use of Lactobcillus casei Shirota or placebo, randomized in a 1:1 ratio. We hypothesize that use of the Yakult product containing Lactobacillus casei Shirota after 12 weeks of continuous use will increase the level of CD4+ T-cells, at least, 50 cells/mm³. We also propose to investigate several markers of immune response, including T cellular activation and NK cells function, and changes in the intestinal microbiota.
Interventions
DIETARY_SUPPLEMENTFermented Milk Drink Yakult 40
Lactobacillus casei Shirota, with 40 billion bacteria per 80 g (concentration of 5 x 10\^8 CFU/g). Intervention will be used for 12 weeks.
Sponsors
Yakult Honsha Co., LTD
University of Sao Paulo General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female HIV-1 infected patients aged between 18 and 60 years. * Patient on suppressive antiretroviral treatment with poor CD4+ T-cell recovery. * No change in antiretroviral therapy in the last six months or intended change in the next 12 weeks. * Availability for the study procedures during the study period. * Giving informed consent to participate in the study
Exclusion criteria
* Diagnosis of any concomitant infections or diseases that might affect immunity or natural history of HIV-1 infection including active Hepatitis B infection, Hepatitis C infection, diabetes mellitus, neoplasias and autoimmune diseases. * Use of treatments that might affect immunity in the last four weeks including immunomodulators, corticosteroids (only systemic use for two weeks or more), or antineoplasic agents. * History of intolerance or allergy to cow milk or any other component of the study product including lactose intolerance, casein allergy, etc. * Pregnancy, nursing mother or intention of became pregnant during the study period (only female participants). * Unable to safely store the study product at home in the conditions recommended by the manufacturer. * Any other condition that might interfere with the study procedure according to the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase between baseline and after 6 weeks and 12 weeks in the absolute CD4+ T-cell count in active and placebo group. | 12 weeks | Only differences greater than 50 T CD4+ cells/mm³ would be included in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in level of cell activation at week 6 | baseline, week 6 | Cell activation will be accessed by flow cytometry assays in a FACSCanto flow cytometer, using the following monoclonal antibodies: CD3, CD4, CD8, CD38, CCR5, CD69, anti-HLA-DR+ |
| Change from baseline in NK cytototoxic activity against K562 cells at week 6 | baseline, week 6 | NK cell phenotyping and function will be assessed according to Long et al., were subpopulations of NK cells will be assessed by the expression of CD56, CD16 molecules in the CD3-CD14-CD20- population of mononuclear cells. Production of IFNgama and CD103a proteins will be evaluated by flow cytometry in K562 stimulated mononuclear cells |
| Change from baseline in NK cytototoxic activity against K562 cells at week 12 | baseline, week 12 | NK cell phenotyping and function will be assessed according to Long et al., were subpopulations of NK cells will be assessed by the expression of CD56, CD16 molecules in the CD3-CD14-CD20- population of mononuclear cells. Production of IFNgama and CD103a proteins will be evaluated by flow cytometry in K562 stimulated mononuclear cells |
| Change from baseline in Intestinal symptoms score of the Inflammatory Bowel Disease Questionnaire (IBQD) at week 12 | baseline, week 12 | — |
| Change from baseline in level of cell activation at week 12 count | baseline, week 12 | Cell activation will be accessed by flow cytometry assays in a FACSCanto flow cytometer, using the following monoclonal antibodies: CD3, CD4, CD8, CD38, CCR5, CD69, anti-HLA-DR+ |
| Number of participants with adverse events reasonable causal relationship with the study product in active and placebo groups | 12 weeks | — |
| Change from baseline in plasma sCD4 levels at week 6 | baseline, week 6 | CD14 levels will be measured using commercially available kits |
| Change from baseline in plasma sCD4 levels at week 12 | baseline, week 12 | — |
| Change from baseline in the intestinal microbiome in the participants taking Lactobacillus casei Shirota at week 12 | baseline, week 12 | — |
Countries
Brazil
Outcome results
None listed