Pharmacokinetics of Maraviroc and Boosted Atazanavir Dual Regimen in Stable HIV-infected Patients

Study Overview
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Brief Summary
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The purpose of this study is to describe pharmacokinetics of maraviroc (MVC) 300 mg and atazanavir/ritonavir (ATV/r) 200/100 mg QD in HIV-infected stable patients.

Detailed Description
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The rational of this study is to save therapeutic options, toxicity and costs. The available literature shows that antiretroviral regimens that do not include a nucleoside backbone of tenofovir resulted in less bone and kidney toxicity. Atazanavir dosing 200/100 mg qd represents a simplification strategy correlated with virologic efficacy and a reduction of parameters toxicity associated. Maraviroc is suggested as a possible drug associated to PI/r in dual therapies. Even in this case, the available evidence supports the choice of the dosage of 300 mg/day.

Official Title
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Pharmacokinetics of Maraviroc and Boosted Atazanavir Dual Regimen in Stable HIV-infected Patients

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: maraviroc (300 mg QD) + atazanavir/ritonavir (300 and 200 mg /100 mg QD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age>18 years; confirmed HIV-antibodies positivity; signed informed consent; HIV-RNA <20 cp/ml for the last 24 months; no virological failures to PI regimens; no major PI resistance associated mutations; genotypic tropism for CCR5 co-receptor. Exclusion Criteria: active opportunistic infections or neoplasms; need for drugs with known drug-drug interactions with included drugs; liver cirrhosis; any evidence of tropism for CXCR4 or dual infection; pregnancy; self-reported adherence<90%; HBsAg positivity; detectable HCV RNA.

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVC + ATV/r<br>maraviroc (300 mg tablet, 300 mg per day every 24 hours) + atazanavir/ritonavir (300 and 200 mg capsule, 300 and 200 mg per day every 24 hours / 100 mg capsule, 100 mg per day every 24 hours) | Drug: maraviroc (300 mg QD) + atazanavir/ritonavir (300 and 200 mg /100 mg QD)<br>* Phase 1: switch from tenofovir disoproxil fumarate/emtricitabine (200/245 mg QD)+ atazanavir/ritonavir (300 /100 mg QD) to maraviroc (300 mg QD) + atazanavir/ritonavir (300 /100 mg QD). Phase 2: switch from maraviroc (300 mg QD) + atazanavir/ritonavir (300 /100 mg QD) to maraviroc (300 mg QD) + atazanavir/ritonavir (200 /100 mg QD)<br>* Other names: NORVIR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maraviroc (300 mg, QD) + atazanavir/ritonavir (200/100 mg, QD) pharmacokinetic evaluation | Number of participants with maraviroc Ctrough>50ng/ml | within the first 16 weeks after switch | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral suppression evaluation | Number of participants with HIV-RNA<20 cp/ml | week 60 | 
| CD4 count evaluation | Changes in CD4+ count | week 60 | 
| bone density evaluation | Changes in bone mineral density (DEXA femur and spine) | week 60 | 
| bone metabolism markers evaluation | Changes in bone metabolism markers (bALP and vitamin D, PTH) | week 60 | 
| glomerular and tubular renal function evaluation | Changes in proteinuria, glycosuria, phosphaturia and GFR; | week 60 | 
| lipid metabolism markers evaluation | changes in total, HDL, LDL cholesterol and triglycerides | week 60 | 
| bilirubin evaluation | changes in total bilirubin levels | week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maraviroc, atazanavir, ritonavir