HIV-1 Infection
Conditions
Brief summary
The purpose of the study was to evaluate whether the probiotic Visbiome Extra Strength reduces inflammation in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study evaluated whether taking Visbiome Extra Strength by mouth for 24 weeks was safe and well-tolerated for HIV-infected persons on antiretroviral therapy (ART). Probiotics are germs such as yeast or bacteria that are found in food and supplements that are used to improve the health of the digestive system. Many people refer to probiotics as helpful bacteria. These bacteria live in the body and help the body work normally. In some medical conditions, including HIV infection, helpful bacteria are replaced with bacteria that can change the normal intestinal function and increase inflammation. The investigators tested whether giving a probiotic restored normal intestinal function and decreased inflammation.
Detailed description
This was a phase II, randomized, double-blind, two-arm study to evaluate whether there is a significant change in sCD14 after 24 weeks of probiotic Visbiome Extra Strength (ES) therapy, and to determine the safety and tolerability of this agent in HIV-infected participants on stable antiretroviral therapy (ART). Participants were randomized 1:1 to Visbiome ES and placebo arms. Both arms initiated study treatment at Week 2 and took 1 sachet per day for the first 2 weeks and then 1 sachet twice daily for the next 22 weeks. All participants were followed for an additional 12 weeks off study product. The study clinic visits included Entry (Week 0), and Weeks 2, 6, 14, 25, 26, and 38. Plasma for the primary outcome was collected at Weeks 0, 2, 25, and 26. The evaluations of safety (clinical assessment for signs and symptoms, diagnoses, and laboratory tests) were done at Weeks 2, 6, 14, 26, and 38. Currently, the results are entered for the primary outcome measure and select secondary outcomes only. The results on the remaining secondary outcomes will be posted when they become available.
Interventions
From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
DRUGPlacebo
From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Exegi Pharma, LLC
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. NOTE: The term licensed refers to a US FDA-approved kit. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load. \- Currently on continuous antiretroviral therapy (ART) for ≥48 weeks prior to study entry with no change in the ART regimen within the 24 weeks prior to study entry except as noted below. NOTE A: Continuous ART is defined as continuous ART for the 48-week period prior to study entry with no ART interruption longer than 7 consecutive days. NOTE B: Modifications of ART during the 24 weeks prior to study entry are permitted in certain circumstances. For example, the change in formulation (eg, from standard formulation to fixed-dose combination including ART modifications switching from ritonavir- to cobicistat-boosted protease inhibitors or from tenofovir disoproxil fumarate to tenofovir alafenamide) is allowed within 24 weeks prior to study entry. A within-class, single-drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 24 weeks prior to study entry, with the exception of a switch between any other NRTI to/from abacavir. No other changes in ART within the 24 weeks prior to study entry are permitted. * No plan to change ART regimen for the study duration. * Screening CD4+ cell count \>200 cells/mm3 obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent. * Screening HIV-1 RNA levels \<50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry. * HIV-1 RNA levels below the limit of quantification using a FDA-approved assay with a quantification limit of 50 copies/mL or lower for at least 48 weeks prior to study entry performed by any laboratory that has a CLIA certification or its equivalent. NOTE: Single determinations that are between the assay quantification limit and 500 copies/mL (ie, blips) are allowed as long as the preceding and subsequent determinations are below the level of quantification. The screening value may serve as the subsequent undetectable value following a blip. * The following laboratory values obtained within 45 days prior to entry by any US laboratory that has a CLIA certification or its equivalent: * Absolute neutrophil count (ANC) ≥1000/mm3 * Hemoglobin ≥10.0 g/dL for men and 9.0 g/dL for women * Platelet count ≥50,000/mm3 * Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit normal (ULN) * Alanine aminotransferase (ALT) (SGPT) ≤5 x ULN * Alkaline phosphatase ≤5 x upper limit normal ULN * Total bilirubin ≤2.5 x ULN (if on atazanavir ≤5 x ULN) * Calculated creatinine clearance (CrCl) \>60 mL/min, as estimated by the Cockcroft-Gault equation. * For females of reproductive potential, negative serum or urine pregnancy test within 45 days prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point-of-care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs. * If participating in sexual activity that could lead to pregnancy, the female study participant must be willing to use a contraceptive while receiving protocol-specified medication. At least one of the following methods MUST be used: * Condoms (male or female), with or without a spermicidal agent * Diaphragm or cervical cap with spermicide * Intrauterine device (IUD) * Hormone-based contraceptive * Ability and willingness of participant or legal guardian/representative to provide informed consent.
Exclusion criteria
\- Initiation of ART during acute HIV infection. NOTE: Participants who initiate ART within 6 months of HIV seroconversion are considered to have been initiated during acute infection and are excluded. \- Receipt of antibiotic therapy within 60 days prior to study entry. NOTE: Antibiotics for opportunistic infection prophylaxis are exclusionary. * Known allergy/sensitivity or any hypersensitivity to components of Visbiome Extra Strength or its formulation. * Use of investigational therapies or investigational vaccines within 90 days prior to study entry. * Non-investigational vaccinations within 2 weeks prior to study entry. * Active drug or alcohol use or dependence that in the opinion of the site investigator would interfere with adherence to study requirements. * Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry. * History of positive HCV antibody with detectable HCV RNA in plasma within 48 weeks prior to study entry. NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to participate. Sites must document negative HCV RNA within 24 weeks of study entry. * History of positive HBsAg within 48 weeks prior to study entry. * Liver cirrhosis, history of inflammatory bowel disease, total colectomy, colon or rectal anastomosis, bowel resection, or current colostomy. * Current diagnosis of diabetes. * Either breastfeeding or pregnant within 24 weeks prior to study entry. * OIs within 45 days prior to study entry. * Use of any of the following medications/products for more than 3 consecutive days within the 60 days prior to study entry: * Immunosuppressives (eg, azathioprine, corticosteroids greater than 20 mg per day \[physiologic replacement doses are allowed\], cyclosporine, mycophenolate, intravenous immunoglobulin (IVIG), interferon, sirolimus, sulfasalazine, tacrolimus). * Immune modulators (eg, cytokines \[eg, IL-2\], granulocyte colony stimulating factor, growth hormone, tumor necrosis factor antagonists, thalidomide). * Antineoplastic agents (except for topical agents for skin cancer). * Probiotics and prebiotics (supplements and products). NOTE: Yogurt with live cultures is allowed. * History of lactose intolerance or milk allergy. * Any episode of acute or persistent diarrhea within 60 days prior to study entry. NOTES: 1. Diarrhea is defined as three or more stools per day that are liquid/loose/watery and will take the shape of a container. If the duration of loose stools meeting this criterion definition is greater than 30 days, this is chronic diarrhea and is not exclusionary. 2. Acute diarrhea is defined as 3-14 day duration. 3. Persistent diarrhea is defined as 15-30 day duration. * Weight loss or gain of more than 25 pounds in the 24 weeks prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in sCD14 From Baseline to Week 25/26 | Weeks 0, 2, 25, and 26 | Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values. Absolute change was calculated as the value at Week 25/26 minus the value at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in IP-10 From Week 2 to Week 26 | Weeks 2 and 26 | All values were log10 transformed prior to calculating change and conducting analyses. Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change. |
| Change in sCD163 From Week 2 to Week 26 | Weeks 2 and 26 | sCD163 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in sTNF-RI From Week 2 to Week 26 | Weeks 2 and 26 | sTNF-RI data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in Oxidized LDL From Week 2 to Week 26 | Weeks 2 and 26 | Oxidized LDL data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26 | Weeks 2 and 26 | Fold change was calculated as the value at Week 26 divided by the value at Week 2. |
| Change in D-dimer From Week 2 to Week 26 | Weeks 2 and 26 | All values were log10 transformed prior to calculating change and conducting analyses. Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change. |
| Change in LPS From Week 2 to Week 26 | Weeks 2 and 26 | LPS data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in LBP From Week 2 to Week 26 | Weeks 2 and 26 | LBP data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in CD4+ Cell Count From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in CD4+/CD8+ Ratio From Week 2 to Week 26. | Weeks 2 and 26 | Fold change was calculated as the value at Week 26 divided by the value at Week 2. |
| Change in %CD14++CD16- From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in %CD14++CD16+ From Week 2 to Week 26 | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in %CD14lowCD16hi From Week 2 to Week 26 | Weeks 2 and 26 | %CD14lowCD16hi data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in %CD4+CD38+ From Week 2 to Week 26. | Weeks 2 and 26 | %CD4+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in IL-6 From Week 2 to Week 26 | Weeks 2 and 26 | IL-6 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in %CD8+CD38+ From Week 2 to Week 26. | Weeks 2 and 26 | %CD8+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in %CD8+HLA-DR+ From Week 2 to Week 26. | Weeks 2 and 26 | %CD8+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
| Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in %CD4+CD28-CD57+ From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in %CD8+CD28-CD57+ From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Change in Chao1 Richness Index From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered. |
| Change in Shannon Diversity Index From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered. |
| Change in Chao1 Richness Index From Week 26 to Week 38. | Weeks 26 and 38 | Absolute change was calculated as the value at Week 38 minus the value at Week 26. Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered. |
| Change in Shannon Diversity Index From Week 26 to Week 38. | Weeks 26 and 38 | Absolute change was calculated as the value at Week 38 minus the value at Week 26. Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered. |
| Change in I-FABP From Week 2 to Week 26. | Weeks 2 and 26 | Absolute change was calculated as the value at Week 26 minus the value at Week 2. |
| Safety | Treatment dispensation to Week 38 | Summary of the highest adverse event grade (0-5) for each participant. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used. |
| Tolerability | Treatment dispensation to Week 38 | Tolerability was successfully completing the protocol-defined treatment period. |
| Change in %CD4+HLA-DR+ From Week 2 to Week 26. | Weeks 2 and 26 | %CD4+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Enrollment began in 04/2016 and completed in 12/2016.
Participants by arm
| Arm | Count |
|---|---|
| Visbiome Extra Strength Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily. | 47 |
| Placebo for Visbiome Extra Strength Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily. | 46 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 8 |
Baseline characteristics
| Characteristic | Placebo for Visbiome Extra Strength | Total | Visbiome Extra Strength |
|---|---|---|---|
| Age, Continuous | 51.5 years | 51 years | 51 years |
| Alcohol Status Current | 31 Participants | 60 Participants | 29 Participants |
| Alcohol Status Former | 8 Participants | 23 Participants | 15 Participants |
| Alcohol Status Never | 5 Participants | 8 Participants | 3 Participants |
| Alcohol Status Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| BMI | 26.2 kg/m^2 | 27.1 kg/m^2 | 27.3 kg/m^2 |
| CD4 Count | 714.5 cells/mm^3 | 712 cells/mm^3 | 702 cells/mm^3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 19 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 74 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV-1 RNA <40 copies/mL | 45 Participants | 92 Participants | 47 Participants |
| HIV-1 RNA >=40 copies/mL | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 38 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 26 Participants | 50 Participants | 24 Participants |
| Region of Enrollment Puerto Rico | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 46 Participants | 92 Participants | 46 Participants |
| sCD14 | 2262 ug/L | 2255 ug/L | 2249 ug/L |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 40 Participants | 80 Participants | 40 Participants |
| Smoking Status Current | 10 Participants | 19 Participants | 9 Participants |
| Smoking Status Former | 15 Participants | 38 Participants | 23 Participants |
| Smoking Status Never | 19 Participants | 34 Participants | 15 Participants |
| Smoking Status Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Weight | 81.3 kg | 83.1 kg | 87 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 1 / 46 |
| other Total, other adverse events | 0 / 47 | 0 / 46 |
| serious Total, serious adverse events | 5 / 47 | 2 / 46 |
Outcome results
Primary
Change in sCD14 From Baseline to Week 25/26
Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values. Absolute change was calculated as the value at Week 25/26 minus the value at Baseline.
Time frame: Weeks 0, 2, 25, and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in sCD14 From Baseline to Week 25/26 | 41 ug/L |
| Placebo for Visbiome Extra Strength | Change in sCD14 From Baseline to Week 25/26 | 92.3 ug/L |
p-value: 0.695% CI: [-246, 143.9]t-test, 2 sided
Secondary
Change in %CD14++CD16- From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD14++CD16- data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD14++CD16- From Week 2 to Week 26. | 2.18 Percent of %CD14++CD16- cells |
| Placebo for Visbiome Extra Strength | Change in %CD14++CD16- From Week 2 to Week 26. | -1.25 Percent of %CD14++CD16- cells |
Secondary
Change in %CD14++CD16+ From Week 2 to Week 26
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD14++CD16+ data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD14++CD16+ From Week 2 to Week 26 | 0.81 Percent of %CD14++CD16+ cells |
| Placebo for Visbiome Extra Strength | Change in %CD14++CD16+ From Week 2 to Week 26 | 0.47 Percent of %CD14++CD16+ cells |
Secondary
Change in %CD14lowCD16hi From Week 2 to Week 26
%CD14lowCD16hi data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in %CD4+CD28-CD57+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD4+CD28-CD57+ data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD4+CD28-CD57+ From Week 2 to Week 26. | -0.08 Percent of %CD4+CD28-CD57+ cells |
| Placebo for Visbiome Extra Strength | Change in %CD4+CD28-CD57+ From Week 2 to Week 26. | -0.09 Percent of %CD4+CD28-CD57+ cells |
Secondary
Change in %CD4+CD38+ From Week 2 to Week 26.
%CD4+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD4+CD38+HLA-DR+ data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26. | -0.06 Percent of %CD4+CD38+HLA-DR+ cells |
| Placebo for Visbiome Extra Strength | Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26. | -0.07 Percent of %CD4+CD38+HLA-DR+ cells |
Secondary
Change in CD4+/CD8+ Ratio From Week 2 to Week 26.
Fold change was calculated as the value at Week 26 divided by the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in CD4+/CD8+ Ratio From Week 2 to Week 26. | 1.03 ratio |
| Placebo for Visbiome Extra Strength | Change in CD4+/CD8+ Ratio From Week 2 to Week 26. | 1.05 ratio |
p-value: 0.4195% CI: [-0.08, 0.04]t-test, 2 sided
Secondary
Change in CD4+ Cell Count From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in CD4+ Cell Count From Week 2 to Week 26. | 9.8 cells/mm^3 |
| Placebo for Visbiome Extra Strength | Change in CD4+ Cell Count From Week 2 to Week 26. | 42.4 cells/mm^3 |
p-value: 0.2995% CI: [-93.5, 28.2]t-test, 2 sided
Secondary
Change in %CD4+HLA-DR+ From Week 2 to Week 26.
%CD4+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in %CD8+CD28-CD57+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD8+CD28-CD57+ data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD8+CD28-CD57+ From Week 2 to Week 26. | 0.77 Percent of %CD8+CD28-CD57+ cells |
| Placebo for Visbiome Extra Strength | Change in %CD8+CD28-CD57+ From Week 2 to Week 26. | -1.50 Percent of %CD8+CD28-CD57+ cells |
Secondary
Change in %CD8+CD38+ From Week 2 to Week 26.
%CD8+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD8+CD38+HLA-DR+ data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26. | 0.19 Percent of %CD8+CD38+HLA-DR+ cells |
| Placebo for Visbiome Extra Strength | Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26. | -0.13 Percent of %CD8+CD38+HLA-DR+ cells |
Secondary
Change in %CD8+HLA-DR+ From Week 2 to Week 26.
%CD8+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in Chao1 Richness Index From Week 26 to Week 38.
Absolute change was calculated as the value at Week 38 minus the value at Week 26. Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered.
Time frame: Weeks 26 and 38
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 26 and Week 38 Chao1 richness index data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in Chao1 Richness Index From Week 26 to Week 38. | 23 Estimator of species richness |
| Placebo for Visbiome Extra Strength | Change in Chao1 Richness Index From Week 26 to Week 38. | -14.1 Estimator of species richness |
Secondary
Change in Chao1 Richness Index From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2. Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 Chao1 richness index data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in Chao1 Richness Index From Week 2 to Week 26. | 48.8 Estimator of species richness |
| Placebo for Visbiome Extra Strength | Change in Chao1 Richness Index From Week 2 to Week 26. | 78.2 Estimator of species richness |
Secondary
Change in D-dimer From Week 2 to Week 26
All values were log10 transformed prior to calculating change and conducting analyses. Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 D-dimer data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in D-dimer From Week 2 to Week 26 | 1.203 Fold change |
| Placebo for Visbiome Extra Strength | Change in D-dimer From Week 2 to Week 26 | 0.937 Fold change |
p-value: 0.0995% CI: [-3.6, 71]t-test, 2 sided
Secondary
Change in I-FABP From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 I-FABP data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in I-FABP From Week 2 to Week 26. | 0.59 ng/mL |
| Placebo for Visbiome Extra Strength | Change in I-FABP From Week 2 to Week 26. | 0.83 ng/mL |
Secondary
Change in IL-6 From Week 2 to Week 26
IL-6 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in IP-10 From Week 2 to Week 26
All values were log10 transformed prior to calculating change and conducting analyses. Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 IP-10 data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in IP-10 From Week 2 to Week 26 | 1.05 Fold change |
| Placebo for Visbiome Extra Strength | Change in IP-10 From Week 2 to Week 26 | 0.94 Fold change |
Secondary
Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26
Fold change was calculated as the value at Week 26 divided by the value at Week 2.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26 | 1.039 ratio |
| Placebo for Visbiome Extra Strength | Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26 | 0.997 ratio |
p-value: 0.5195% CI: [-0.09, 0.17]t-test, 2 sided
Secondary
Change in LBP From Week 2 to Week 26
LBP data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in LPS From Week 2 to Week 26
LPS data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in Oxidized LDL From Week 2 to Week 26
Oxidized LDL data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in sCD163 From Week 2 to Week 26
sCD163 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Change in Shannon Diversity Index From Week 26 to Week 38.
Absolute change was calculated as the value at Week 38 minus the value at Week 26. Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered.
Time frame: Weeks 26 and 38
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 26 and Week 38 Shannon diversity index data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in Shannon Diversity Index From Week 26 to Week 38. | -0.10 Estimator of species richness & evenness |
| Placebo for Visbiome Extra Strength | Change in Shannon Diversity Index From Week 26 to Week 38. | 0.03 Estimator of species richness & evenness |
Secondary
Change in Shannon Diversity Index From Week 2 to Week 26.
Absolute change was calculated as the value at Week 26 minus the value at Week 2. Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the types that are considered.
Time frame: Weeks 2 and 26
Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 Shannon diversity index data were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visbiome Extra Strength | Change in Shannon Diversity Index From Week 2 to Week 26. | 0.11 Estimator of species richness & evenness |
| Placebo for Visbiome Extra Strength | Change in Shannon Diversity Index From Week 2 to Week 26. | 0.13 Estimator of species richness & evenness |
Secondary
Change in sTNF-RI From Week 2 to Week 26
sTNF-RI data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.
Time frame: Weeks 2 and 26
Population: These data were not assayed and the analysis was abandoned.
Secondary
Safety
Summary of the highest adverse event grade (0-5) for each participant. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Time frame: Treatment dispensation to Week 38
Population: All enrolled participants who initiated study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Visbiome Extra Strength | Safety | Grade 0 | 32 Participants |
| Visbiome Extra Strength | Safety | Grade 1 | 3 Participants |
| Visbiome Extra Strength | Safety | Grade 2 | 5 Participants |
| Visbiome Extra Strength | Safety | Grade 3 | 5 Participants |
| Visbiome Extra Strength | Safety | Grade 4 | 2 Participants |
| Visbiome Extra Strength | Safety | Grade 5 | 0 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 4 | 0 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 0 | 35 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 3 | 3 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 1 | 3 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 5 | 1 Participants |
| Placebo for Visbiome Extra Strength | Safety | Grade 2 | 1 Participants |
p-value: 0.15Kruskal-Wallis
Secondary
Tolerability
Tolerability was successfully completing the protocol-defined treatment period.
Time frame: Treatment dispensation to Week 38
Population: All enrolled participants who initiated study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Visbiome Extra Strength | Tolerability | Completed as defined by protocol | 43 Participants |
| Visbiome Extra Strength | Tolerability | Did not complete as defined by protocol | 4 Participants |
| Placebo for Visbiome Extra Strength | Tolerability | Did not complete as defined by protocol | 12 Participants |
| Placebo for Visbiome Extra Strength | Tolerability | Completed as defined by protocol | 31 Participants |