Bone, Inflammation, Gut and Renal Biomarkers in Antiretroviral Naïve HIV-1 Positive Subjects

Study Overview
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Brief Summary
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Co-morbidities, including low bone mineral density, increased visceral adiposity and chronic kidney disease (CKD) are frequent in people living with HIV, and may be driven by ongoing inflammation and immune activation. Initiation of ART reduces inflammation and immune activation and is associated with changes in bone and renal biomarkers and gut microbiota. Investigators hypothesise that changes in gut microbiome when starting antiretroviral therapy correlate to changes in bone and renal biomarkers and wish to explore possible mechanisms linking these by investigating changes in markers of inflammation and immune activation.

Official Title
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Bone, Inflammation, Gut and Renal Biomarkers in Antiretroviral Naïve HIV-1 Positive Subjects Commencing Antiretroviral Therapy: the BIGgeR Study.

Conditions
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HIV Positive

Intervention / Treatment
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* Other: blood and urinary samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 positive Age 18-64 years Able to give informed consent Not previously treated for chronic HIV-1 infection, except for pre- or post- exposure prophylaxis exposure or treatment for mother to child transmission >12 months ago Due to commence antiretroviral therapy by treating clinician Exclusion Criteria: - Previous major intestinal surgery/inflammatory bowel conditions Infective diarrhoea in the last 3 months BMI<18.5 Currently pregnant OR planning to conceive during the study period Previous use of antiretroviral therapy, except for pre- or post- exposure prophylaxis exposure or treatment for mother to child transmission >12 months ago Use of antibiotics (except for prophylactic co-trimoxazole) within the last 2 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Blood and urinary sample<br>Blood and urinary sample in HIV 1 positive adults initiating treatment | Other: blood and urinary samples<br>* blood samples, rectal and urethral swabs , urine samples at inclusion, after 4 weeks then 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| faecal microbial alpha-diversity | Change in faecal microbial alpha-diversity (change in mean Shannon Diversity Index score in faecal microbiota) . | At 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| markers of gut epithelium integrity | Change in markers of gut epithelium integrity and bacterial translocation | At 12 weeks | 
| inflammatory marker | Change in inflammatory marker (c-reactive protein) | at 12 weeks | 
| circulating markers of monocyte activation | Change in circulating marker of monocyte activation | at 12 weeks | 
| renal glomerular biomarkers | Change in renal glomerular biomarker (KIM-1) | at 12 weeks | 
| bone biomarkers | Change in bone biomarkers | at 12 weeks |