Probiotics for Cardiovascular Disease in HIV+ Individuals

(META HIV CVD Trial)

Overseen By Emily Smith, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Not fluent in English

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

250 Participants Needed

Trial Summary

What is the purpose of this trial?

Among people living with HIV, heavy drinking increases the risk of heart disease and death. Studies suggest that alcohol changes the number and kind of bacteria in your gut and these changes increase the risk of heart disease and death. This randomized controlled trial will determine whether a pill containing healthy gut bacteria can increase the number good bacteria in the gut, lower levels of inflammation, and lower the risk of heart disease and death.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Probiotics for Cardiovascular Disease in HIV+ Individuals?

Research suggests that probiotics may help reduce inflammation and improve immune function in people living with HIV, which could potentially lower cardiovascular risk. In animal studies, certain probiotic strains have shown promise in reducing heart damage and improving heart health. ^{1 2 3 4 5}

Is it safe for HIV+ individuals to take probiotics for cardiovascular health?

Research on probiotics in HIV+ individuals shows they are generally safe, with studies indicating no significant adverse events. Probiotics have been used to manage inflammation and improve gut health in HIV patients, suggesting they are well-tolerated. ^{1 2 4 5 6}

How is the probiotic treatment for cardiovascular disease in HIV+ individuals different from other treatments?

This probiotic treatment is unique because it focuses on modulating the gut microbiota (the community of microorganisms in the intestines) to reduce inflammation and immune activation, which are linked to cardiovascular disease in HIV+ individuals. Unlike traditional cardiovascular treatments, this approach uses beneficial bacteria to potentially improve gut health and immune function. ^{1 3 4 7 8}

Eligibility Criteria

This trial is for individuals living with HIV who are fluent in English. It's designed to help those who drink heavily and are at increased risk of heart disease and death due to changes in gut bacteria caused by alcohol.

Inclusion Criteria

HIV infected

Exclusion Criteria

I am not fluent in English.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a probiotic tailored to alcohol-associated gut dysbiosis or a placebo for 6 months

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements of inflammation, microbial translocation, and cardiovascular risk

6 months

Bi-monthly visits (in-person)

Extension

Optional continuation of monitoring for long-term effects on cardiovascular and mortality risk

6 months

Treatment Details

Interventions

• Placebo
• Probiotic

Trial Overview The study tests if a probiotic pill, which contains healthy gut bacteria, can boost the number of good bacteria in the gut, reduce inflammation, and lower heart disease risk compared to a placebo (a pill with no active ingredients).

Participant Groups

Group I: Study Supplement Experimental Treatment 1 Intervention

Probiotic

Group II: Study placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

University of Louisville

Collaborator

Trials

353

Recruited

76,400+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

Findings from Research

In a phase 2b trial involving 29 HIV-positive individuals with low CD4+ T-cell counts, probiotic supplementation (De Simone Formulation Probiotic) did not significantly reduce immune activation markers compared to placebo after 48 weeks.

Interestingly, while CD4+ T-cell activation decreased in the placebo group, it increased in the probiotic group, suggesting that the probiotic may not be beneficial and could potentially lead to increased immune activation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. Rousseau, RK., Walmsley, SL., Lee, T., et al.[2022]

In a rat model of systemic inflammatory response syndrome (SIRS), probiotics Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) significantly reduced myocardial infarction size, suggesting a protective effect against ischemic-reperfusion injury.

The treatment with these probiotics also normalized various inflammatory and immune parameters, indicating their potential to improve cardiovascular health in the context of metabolic and inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. Borshchev, YY., Sonin, DL., Burovenko, IY., et al.[2023]

In a study of 45 HIV-infected individuals, taking the probiotic Lactobacillus rhamnosus GG (LGG) for 8 weeks significantly reduced intestinal inflammation, as shown by PET/MRI scans.

LGG supplementation also led to a decrease in harmful gut bacteria, specifically Enterobacteriaceae, suggesting a potential mechanism for its anti-inflammatory effects in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals. Arnbjerg, CJ., Vestad, B., Hov, JR., et al.[2022]

Current evidence from 16 clinical studies, including randomized control trials, does not support the use of probiotics to reduce inflammation in people living with HIV, as no consistent improvements were observed in inflammation markers or CD4 counts.

While some studies suggested potential benefits of probiotics, the overall results were inconsistent, indicating that further research is needed to explore their effects in ART-treated individuals at high risk for inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics to manage inflammation in HIV infection. Reikvam, DH., Meyer-Myklestad, MH., Trøseid, M., et al.[2021]

A systematic review and meta-analysis of 16 randomized controlled trials involving probiotics, prebiotics, and synbiotics found no significant improvement in CD4+ T-cell counts in HIV-infected patients compared to placebo, indicating limited efficacy of these supplements.

Subgroup analysis revealed a significant increase in CD4 counts in studies with a high risk of bias, suggesting that the overall evidence is insufficient and that more rigorous research is needed to clarify the effects of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis. Fu, YS., Chu, QS., Ashuro, AA., et al.[2022]

Probiotic supplementation significantly improved CD4+ T-cell counts in HIV-infected children, with a mean increase of 123.92 cells/mm³, indicating a potential benefit in managing HIV-related immune issues.

No adverse effects were reported from probiotic use, suggesting that they are a safe adjunct therapy alongside standard antiretroviral treatment (ART) for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sachdeva, M., Sra, HK., Agarwal, A., et al.[2022]

Current research indicates that while gut microbiota disturbances are linked to cardiovascular disease in HIV-infected individuals, there is a lack of clinical trials directly assessing the impact of prebiotics, probiotics, symbiotics, and fecal transplantation on reducing cardiovascular disease risk in these patients.

The review of 38 clinical trials highlights significant variability in the types, doses, and durations of these interventions, making it challenging to establish clear guidelines for their use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients. Villoslada-Blanco, P., Pérez-Matute, P., Oteo, JA.[2021]

Probiotic administration may help protect the gut and delay the progression of HIV-1 to AIDS by stabilizing CD4+ T cell numbers and reducing inflammation, as shown in various studies over the past five years.

Supplementation with specific probiotics, like Bifidobacterium lactis, has been linked to improved growth in infants with congenital HIV-1 infection and has shown promise in enhancing immune responses and reducing chronic immune activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection. Cunningham-Rundles, S., Ahrné, S., Johann-Liang, R., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Probiotics to manage inflammation in HIV infection. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection. [2021]