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

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

Objectives of the study:

1. 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.
2. To collect relevant information about the safety, the immunologic and the economic impact of this strategy.

Study Overview

• Status: Terminated
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Maraviroc, Darunavir/r; Drug: current antiretroviral therapy with 3 drugs

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Catholic University Of Sacred Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MARAVIROC, DARUNAVIR/r; 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; Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg
Sham Comparator: current ART with 3 drugs; Patients on HAART with three drugs and HIV RNA below 50 copies/mL	Drug: current antiretroviral therapy with 3 drugs; To continue the assumption of previous HAART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Andrea De Luca, Prof, Catholic University of the Sacred Heart

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 3, 2011
• First Submitted That Met QC Criteria: June 3, 2011
• First Posted (Estimate): June 7, 2011

Study Record Updates

• Last Update Posted (Estimate): February 8, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: HIV; AIDS; Treatment experienced; Darunavir; Maraviroc; Simplification; Tropism; Highly Active AntiRetroviral Therapy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc; Darunavir; Anti-Retroviral Agents
• Other Study ID Numbers: 2010-023316-13