Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and efficacy of a novel combination antiretroviral therapy regimen consisting of maraviroc plus darunavir/ritonavir in treatment-naive patients infected with R5-tropic HIV-1. The hypothesis is that in treatment-naive subjects infected with R5-tropic HIV-1, combination antiretroviral therapy with maraviroc plus darunavir/ritonavir is well tolerated and efficacious.

Official Title
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Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile

Conditions
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HIV-1 Infection, HIV Infections

Intervention / Treatment
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* Drug: maraviroc
* Drug: darunavir
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection, as documented by any licensed HIV test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA any time prior to study entry Plasma HIV-1 RNA 5, 000 to 500,000 copies/mL obtained within 90 days prior to study entry Exclusive R5 tropism based on enhanced sensitivity Trofile assay done within 90 days prior to entry CD4 cell count > 100 cells/mm3 within 90 days prior to study entry HIV genotype (for RT and protease) performed at any time before study entry (Subjects with single or combination NNRTI or NRTI RAM(s) at screening are permitted) ARV drug-naïve, defined as no previous ARV treatment at any time prior to study entry Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry Negative result from a hepatitis C antibody test performed within 90 days prior to study entry Laboratory values obtained within 30 days prior to study entry: ANC >=750/mm3 Hemoglobin >=10 g/dL Platelets >=50,000/mm3 AST (SGOT), ALT (SGPT), and alkaline phosphatase <=5 x ULN Calculated creatinine clearance (CrCl) >=30 mL/min, as estimated by the Cockcroft-Gault equation* Negative serum or urine pregnancy test within 48 hours prior to study entry for women with reproductive potential If participating in sexual activity that could lead to pregnancy, the study subjects with reproductive potential must use one form of contraceptive while receiving protocol-specified medications and for 60 days after stopping the medications. Men and women age >=18 years Ability and willingness of subject or legal guardian/representative to provide informed consent Exclusion Criteria: Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry Screening HIV genotype obtained any time prior to study entry with any DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V) Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy. NOTE: Subjects receiving stable physiologic glucocorticoid doses (defined as prednisone ≤10 mg/day [or equivalent] as a stable or tapering dose) are permitted. Subjects receiving corticosteroids for acute therapy for PCP or asthma exacerbation, or receiving a short course (defined as ≤2 weeks of pharmacologic glucocorticoid therapy) are permitted Breast-feeding Requirement for any medication that is prohibited with a study medication Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion Active drug or alcohol use or dependence that could interfere with adherence to study requirements

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: Maraviroc plus darunavir/ritonavir<br>Single arm open label trial of maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily for 96 weeks | Drug: maraviroc<br>* 150 mg tab by mouth once daily for 96 weeks<br>* Other names: Selzentry;Drug: darunavir<br>* 800 mg tab by mouth once daily for 96 weeks<br>* Other names: Prezista;Drug: ritonavir<br>* 100 mg capsule by mouth once daily for 96 weeks<br>* Other names: norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma HIV-1 RNA >50 | Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virologic Failure or Off Study Treatment Regimen | Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA > 50 copies/mL) or off study treatment regimen (composite end point) | 24 weeks | 
| Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL | Percentage of participants with confirmed plasma HIV-1 RNA level >50 copies/mL | 48 weeks | 
| Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher | Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen | 96 weeks | 
| Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES |  | At study entry and at the time of virologic failure | 
| Drug Adherence, Number of Participants With Missed Doses | Drug adherence, assessed as number of participants with missed doses over four-day recall | Week 24 | 
| Trough Concentrations (Ctrough) of Maraviroc | Average trough concentration (Ctrough) of maraviroc | 24 hours | 
| Median CD4 Count Change From Baseline | Median changes from baseline in peripheral CD4+ T-cell count | 96 weeks | 
| Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL | Proportion of participants with confirmed plasma HIV-1 RNA level >50 copies/mL | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment naive