Improving Prognosis in HIV Infection

Study Overview
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Brief Summary
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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.

Official Title
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Adjuvant Mucosal Therapy in HIV-infected Men With Insufficient Response to Antiretroviral Therapy

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Dietary Supplement: Probiotic compound


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic compound<br>Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium animalis subsp. lactis, and Streptococcus thermophilus. | Dietary Supplement: Probiotic compound<br>* Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium animalis subsp. lactis, and Streptococcus thermophilus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Effects | Number of Participants who Experienced Adverse Effects | 10 weeks | 
| Delta HIV Viral Load | Unit og Measure: copies/mL | 8 weeks | 
| Delta Blood CD4 Count | Unit of Measure: cells/microL | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alteration in Gut Microbiota Composition | Explorative (Unit of Measure: Descriptive) | 8 weeks | 
| Alterations in Epithelial Gene Expression | Explorative (Unit of Measure: Descriptive) | 8 weeks | 
| Alterations in Lamina Propria T Cell Subsets | Explorative assays on T cell subsets distribution and function (Unit of Measure: Frequency) | 8 weeks | 
| Alterations in Systemic T Cell Intracellular Signaling | Explorative assays on T cell receptor signaling mechanism (Unit of Measure: Frequency) | 8 weeks | 
| Alterations in Systemic Markers of Immune Activation | Explorative assays on soluble inflammation markers and lymphoid cells activation status (Unit of Measure: Descriptive) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Probiotics, Microbiota, Mucosal immunology, Gut biopsy