Human Immunodeficiency Virus
Conditions
Keywords
HIV, Probiotics, Microbiota, Mucosal immunology, Gut biopsy
Brief summary
The primary objective of this study is to assess the safety of probiotics in cART-treated immunologic non-responder (INR) patients with chronic HIV infection. The secondary objectives are to i) explore the biological effects of probiotics in combined antiretroviral therapy(cART)-treated INR patient with chronic HIV infection, and ii) investigate differences between cART-treated HIV-infected INR and non-INR patients with regards to gut microbial composition and mucosal barrier function.
Interventions
DIETARY_SUPPLEMENTProbiotic compound
Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium animalis subsp. lactis, and Streptococcus thermophilus.
Sponsors
University of Oslo
Oslo University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
25 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* HIV seropositive \>4 years. * Continuous combined antiretroviral treatment (cART) \>4 years. * Plasma HIV RNA \<50 copies/mL \>3,5 years. * Cluster of differentiation(CD)4+ T cell count \<400 cells/µL (OR \>600 cells/µl) \>3.5 years. * Caucasian * Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations.
Exclusion criteria
* Plasma hepatitis C (HCV) RNA positive. * Serum hepatitis B surface antigen (HBsAg) positive. * Comorbidity of inflammatory bowel disease, coeliac disease or malnutrition. * Concomitant use of non-steroid anti-inflammatory drugs (NSAID), corticosteroids, disease-modifying antirheumatic drugs, or other anti-inflammatory pharmaceutical substances. * Concomitant use of antithrombotic pharmaceutical substances * Regular (weekly) use of any probiotic substance within 3 months prior to inclusion. * Use of antibiotics within 3 months prior to inclusion. * Deranged liver function (serum albumin \<25 g/L or Child-Pugh ≥10) * Renal failure (estimated glomerular filtration rate (eGFR) \<30 ml/min) * Heart failure (NYHA class II-IV) * Intolerance to milk or phenylalanine * Any reason why, in the opinion of the investigator, the patient should not participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Effects | 10 weeks | Number of Participants who Experienced Adverse Effects |
| Delta HIV Viral Load | 8 weeks | Unit og Measure: copies/mL |
| Delta Blood CD4 Count | 8 weeks | Unit of Measure: cells/microL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alterations in Systemic T Cell Intracellular Signaling | 8 weeks | Explorative assays on T cell receptor signaling mechanism (Unit of Measure: Frequency) |
| Alteration in Gut Microbiota Composition | 8 weeks | Explorative (Unit of Measure: Descriptive) |
| Alterations in Systemic Markers of Immune Activation | 8 weeks | Explorative assays on soluble inflammation markers and lymphoid cells activation status (Unit of Measure: Descriptive) |
| Alterations in Epithelial Gene Expression | 8 weeks | Explorative (Unit of Measure: Descriptive) |
| Alterations in Lamina Propria T Cell Subsets | 8 weeks | Explorative assays on T cell subsets distribution and function (Unit of Measure: Frequency) |
Countries
Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Probiotic Intervention HIV positive on cART \>4 years with CD4 \<400 cells/ml and HIV RNA \<50 copies/ml | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Probiotic Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 49 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants |
| HBsAg negative AND HCV RNA negative AND no gastrointestinal disorders | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Norway | 20 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Adverse Effects
Number of Participants who Experienced Adverse Effects
Time frame: 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Probiotic Intervention | Adverse Effects | 1 Participants |
Primary
Delta Blood CD4 Count
Unit of Measure: cells/microL
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Probiotic Intervention | Delta Blood CD4 Count | 18 cells/microL |
Primary
Delta HIV Viral Load
Unit og Measure: copies/mL
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Probiotic Intervention | Delta HIV Viral Load | 0 copies/mL |
Secondary
Alteration in Gut Microbiota Composition
Explorative (Unit of Measure: Descriptive)
Time frame: 8 weeks
Secondary
Alterations in Epithelial Gene Expression
Explorative (Unit of Measure: Descriptive)
Time frame: 8 weeks
Secondary
Alterations in Lamina Propria T Cell Subsets
Explorative assays on T cell subsets distribution and function (Unit of Measure: Frequency)
Time frame: 8 weeks
Secondary
Alterations in Systemic Markers of Immune Activation
Explorative assays on soluble inflammation markers and lymphoid cells activation status (Unit of Measure: Descriptive)
Time frame: 8 weeks
Secondary
Alterations in Systemic T Cell Intracellular Signaling
Explorative assays on T cell receptor signaling mechanism (Unit of Measure: Frequency)
Time frame: 8 weeks