MARCH Renal Substudy

Study Overview
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Brief Summary
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Chronic kidney disease (CKD) is an emerging problem in patients with treated HIV. Antiretroviral therapy associated renal dysfunction has been predominantly described in terms of reduced glomerular filtration (eGFR). Proteinuria is a key component of CKD and may occur in the absence of significant reductions in eGFR. This substudy is an exploration of changes in urinary protein excretion in a randomised, open-label study to evaluate the efficacy and safety of MVC as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (PI/r) in HIV-1 infected individuals with stable, well-controlled plasma HIV-RNA while taking their first N(t)RTI + PI/r regimen of combination antiretroviral therapy (cART).

Detailed Description
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The aim of this substudy of MARCH is to characterize the changes in protein and salt excretion through the kidney utilising the randomised arms of the parent study MARCH. The investigators hypothesize there will be an improvement in proteinuria in those switching to maraviroc containing regimens.

Official Title
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Maraviroc Switch Collaborative Study Renal Substudy

Conditions
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Proteinuria, HIV

Intervention / Treatment
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* Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors
* Drug: Arm 2 boosted protease inhibitors and maraviroc
* Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written, informed consent for participation in the substudy Enrolled into the substudy either at or before the week 0 visit of the main study

Ages Eligible for Study
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Minimum Age: 18 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

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NRTI + PI<br>arm 1 | Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors<br>* NRTI + PI<br>* Other names: ritonavir;|
| Active Comparator: PI + maraviroc<br>arm 2 | Drug: Arm 2 boosted protease inhibitors and maraviroc<br>* PI + maraviroc<br>* Other names: ritonavir;|
| Active Comparator: NRTI + maraviroc<br>arm 3 | Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc<br>* NRTI + maraviroc<br>* Other names: lamivudine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in proteinuria and albuminuria between baseline and week 96 | To compare the change in protein and albumin excretion as measured by the urine PCR and ACR through the kidneys between the randomised and standard of care (control) arm of MARCH. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in renal tubular function between baseline and week 96 | To evaluate the following aspects of renal function at baseline and changes within and between study groups: Tubular function defined as proximal tubular function; ascending thick loop of Henle; distal tubular function; volume and renal potassium handling; Non-tubular function i.e. eGFR; Urine albumin:creatinine ratio; Determine factors associated with renal dysfunction within the cohort e.g. demographics, HIV related, HIV-treatment related, co-morbidities, concomitant medication (such as ACE inhibitors and ARB; PI/r co-administered with TDF); TDF use; | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proteinuria, HIV