Synbiotics in Advanced HIV Infection

Study Overview
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Brief Summary
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Late diagnosed HIV-infected subjects show impaired immunological recovery resulting in a greater risk of clinical progression. Gut bacteria metabolism appears to impact immune recovery in HIV-infected subjects, and while nutritional interventions with prebiotics and probiotics seem to exert immunological effects, the clinical implications in this key population remain unknown. This is a pilot multicenter randomized placebo-controlled, double blind clinical trial in HIV-infected ART-naive subjects with <350 CD4 T cells/mm3 or AIDS. Participants will be randomized (1:1) to either the synbiotic nutritional supplement PMT25341 or placebo for 48 weeks, each in combination with first-line ART. Primary outcomes will be safety and immunological recovery. Secondary outcomes will include changes in fecal microbiota structure and plasma inflammatory markers.

Official Title
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Immunological Effects of an Immunomodulatory Synbiotic Intervention at Advanced HIV Disease

Conditions
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HIV Infection Asymptomatic

Intervention / Treatment
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* Dietary Supplement: PMT25341
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected ART-naive subjects with <350 CD4 T cells/mm3 or AIDS Initiating ART with any first-line regimen recommended in the Spanish GESIDA National Guidelines Exclusion Criteria: Age <18 years Pregnancy Type 1 or 2 diabetes End-stage renal disease Lactose intolerance Use of immunomodulatory drugs Neutrophil count <750cells/uL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PMT25341<br>A mixture of prebiotics, probiotics, oligonutrients, essential aminoacids, omega-3 fatty acids | Dietary Supplement: PMT25341<br> <br> |
| Placebo Comparator: PLACEBO<br>Lactose | Dietary Supplement: Placebo<br>* Lactose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | From baseline through week 48 | 
| Changes in CD4+ T cell counts/uL |  | From baseline through week 48 | 
| Changes in CD8+ T cell counts/uL |  | From baseline through week 48 | 
| Changes in CD4/CD8 ratio |  | From baseline through week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota composition: alpha-diversity |  | From baseline through week 48 | 
| Microbiota composition: Unifrac distances |  | From baseline through week 48 | 
| Microbiota composition: Canberra distances |  | From baseline through week 48 | 
| Changes in plasma soluble CD14 levels |  | From baseline through week 48 | 
| Changes in plasma hs-CRP levels |  | From baseline through week 48 | 
| Changes in plasma IFABP levels |  | From baseline through week 48 | 
| Changes in plasma lipoteichoic acid levels |  | From baseline through week 48 | 
| Changes in plasma kynurenine/tryptophan ratio |  | From baseline through week 48 | 
| Changes in percentage of HLADR+/CD38+ T cells |  | From baseline through week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, immunologic recovery, microbiota, prebiotics, probiotics, synbiotics