Switch to Darunavir/r + Maraviroc Quaque Die in Patients With R5 Tropism by Viral DNA Genotyping (GUSTA)

Study Overview
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Brief Summary
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Objectives of the study: To verify the safety and the efficacy of the study treatment, defined as the persistent control of the virus' replication at 48 weeks after the simplification to maraviroc + darunavir with ritonavir in patients with R5 tropism by viral DNA genotyping. To collect relevant information about the safety, the immunologic and the economic impact of this strategy.

Official Title
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Switch to Darunavir/r + Maraviroc QD in Patients With R5 Tropism by Viral DNA Genotyping With Suppressed Viremia (GUSTA): a Multicenter, Open-label, Randomized Controlled Trial

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Maraviroc, Darunavir/r
* Drug: current antiretroviral therapy with 3 drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated with the same regimen including 3 HAART from at least 4 months Aged 18 years or older Who gave informed consent to the participation to the study With at least two viral load < 50 copies/mL in two consecutive determinations at least 6 months apart (tolerance of two weeks) With CD4 cell count > 200 cells/μL and absence of any opportunistic infection or AIDS-related disease for at least one year prior to the screening. With R5 tropism by viral DNA genotyping (geno2pheno clonal) With CD4 cell count nadir>50 cell/mmc or 100 cell/mmc if previous enfuvirtide or integrase inhibitors use Exclusion Criteria: With at least one major or two minor mutation conferring resistance to darunavir reported in the update list of International AIDS Society - USA , in previous resistance test Previous D/M or X4 viral tropism Previous major clinical toxicities (grade >=3) to the proposed drugs of the study Pregnancy or breast feeding, desire of pregnancy in the short term Past exposure to Chemokine Receptor 5 antagonist HBsAg serostatus Liver cirrhosis of class C (Child-Pugh) Sulpha drug hypersensitivity The presence of major non AIDS-defining diseases that, in the opinion of the investigator, may compromise the retention of the patient in the study for the necessary follow-up period. Estimated glomerular filtration < 30 ml/min (cockroft-Gaut; MDRD formula if black-African or african-american) at screening visit Hypertransaminasemia of grade IV (more than 10 times the upper normal limit) at screening visit

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MARAVIROC, DARUNAVIR/r<br>Treatment simplification from a standard combined antiretroviral therapy including 3 drugs to Maraviroc plus Darunavir with Ritonavir. Treatment simplification from three-drugs- to two-drugs-based antiretroviral therapy | Drug: Maraviroc, Darunavir/r<br>* Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg<br>|
| Sham Comparator: current ART with 3 drugs<br>Patients on HAART with three drugs and HIV RNA below 50 copies/mL | Drug: current antiretroviral therapy with 3 drugs<br>* To continue the assumption of previous HAART<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with virological failure (two consecutive measures of HIV-RNA higher than 50 copies/mL or a single measure higher than 1000 copies/mL) within 48 weeks at per protocol analysis, with switch=failure |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with virological failure (two consecutive measures of HIV-RNA higher than 50 copies/mL or a single measure higher than 1000 copies/mL) within 96 weeks at intention-to treat analysis with missing value=Failure |  | 96 weeks | 
| Time to virological failure at survival analysis |  | 48 weeks | 
| Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping) |  | 48 weeks | 
| Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks |  | 96 weeks | 
| Evolution of adherence and quality of life after 24, 48 and 96 weeks |  | 96 weeks | 
| Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks |  | 96 weeks | 
| Evolution of metabolic parameters at 96 weeks |  | 96 weeks | 
| Change of the results of neurocognitive tests at 48 and 96 weeks |  | 96 weeks | 
| Modification of bone density and subcutaneous fat at 48 and 96 weeks |  | 96 weeks | 
| Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks |  | 96 weeks | 
| Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy |  | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, AIDS, Highly Active AntiRetroviral Therapy, Simplification, Maraviroc, Darunavir, Treatment experienced, Tropism