Immune Reconstitution in HIV Disease (IREHIV)

Study Overview
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Brief Summary
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The aim with this study is to provide immunotherapy with vitamin D and phenylbutyrate to treatment-naive HIV infected patients to induce important antimicrobial defence mechanisms and decreased inflammation.

Official Title
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Immune Reconstitution in HIV Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
* Drug: Placebo tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients >18 years not subjected to HAART. HIV-1 infected patients with CD4 T cells counts >200 cells/ml. Detectable plasma viral loads >1000 copies/ml. Exclusion Criteria: Patients on HAART or other antimicrobial drugs (including bactrim). Antimicrobial drug treatment in the past month. Patients with medical contra-indication for biopsy such as bleeding tendencies. Hypercalcaemia (serum calcium > 3,0 mmol/L) identified at baseline. Pregnant and breast feeding women. Any known liver or kidney function abnormality, malignancy or patients treated with cardiac glycosides.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)<br>Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks. | Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)<br>* Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.<br>|
| Placebo Comparator: Placebo tablets<br>Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks. | Drug: Placebo tablets<br>* Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV viral load | Plasma HIV viral load will be used to monitor efficacy of vitamin D and phenylbutyrate treatment among treatment-naïve HIV patients at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at 16 weeks compared to baseline (time point 0). | 0 (baseline) compared to 16 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical secondary endpoints | Overall clinical symptoms. Body mass index (BMI). Mid upper arm circumference (MUAC). | 0, 4, 8, 16, 24 weeks. | 
| Laboratory secondary endpoints | HIV viral load (0, 4, 8, 24 weeks). Peripheral CD4/CD8 T cell counts. Plasma levels of vitamin D, LL-37, sCD14, LPS, 16S RNA and cytokine/chemokine profiles. Calprotectin in feces. Inflammation and microbial translocation in colon punch biopsies (0 and 16 weeks). Functional studies of immune cells (PBMCs). | 0, 4, 8, 16, 24 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammation, HIV, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response