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

Primary Purpose

HIV Infection

Status
Terminated
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Maraviroc, Darunavir/r
current antiretroviral therapy with 3 drugs
Sponsored by
Catholic University of the Sacred Heart
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection focused on measuring HIV, AIDS, Highly Active AntiRetroviral Therapy, Simplification, Maraviroc, Darunavir, Treatment experienced, Tropism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Catholic University of Sacred Heart

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

MARAVIROC, DARUNAVIR/r

current ART with 3 drugs

Arm Description

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

Patients on HAART with three drugs and HIV RNA below 50 copies/mL

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Time to virological failure at survival analysis
Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping)
Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks
Evolution of adherence and quality of life after 24, 48 and 96 weeks
Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks
Evolution of metabolic parameters at 96 weeks
Change of the results of neurocognitive tests at 48 and 96 weeks
Modification of bone density and subcutaneous fat at 48 and 96 weeks
Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks
Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy

Full Information

First Posted
June 3, 2011
Last Updated
February 5, 2016
Sponsor
Catholic University of the Sacred Heart
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1. Study Identification

Unique Protocol Identification Number
NCT01367210
Brief Title
Switch to Darunavir/r + Maraviroc Quaque Die in Patients With R5 Tropism by Viral DNA Genotyping (GUSTA)
Acronym
GUSTA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Because a higher rate of virological failures in study versus control arm.
Study Start Date
June 2011 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catholic University of the Sacred Heart

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
Keywords
HIV, AIDS, Highly Active AntiRetroviral Therapy, Simplification, Maraviroc, Darunavir, Treatment experienced, Tropism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
165 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MARAVIROC, DARUNAVIR/r
Arm Type
Experimental
Arm Description
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
Arm Title
current ART with 3 drugs
Arm Type
Sham Comparator
Arm Description
Patients on HAART with three drugs and HIV RNA below 50 copies/mL
Intervention Type
Drug
Intervention Name(s)
Maraviroc, Darunavir/r
Intervention Description
Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg
Intervention Type
Drug
Intervention Name(s)
current antiretroviral therapy with 3 drugs
Intervention Description
To continue the assumption of previous HAART
Primary Outcome Measure Information:
Title
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
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
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
Time Frame
96 weeks
Title
Time to virological failure at survival analysis
Time Frame
48 weeks
Title
Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping)
Time Frame
48 weeks
Title
Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks
Time Frame
96 weeks
Title
Evolution of adherence and quality of life after 24, 48 and 96 weeks
Time Frame
96 weeks
Title
Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks
Time Frame
96 weeks
Title
Evolution of metabolic parameters at 96 weeks
Time Frame
96 weeks
Title
Change of the results of neurocognitive tests at 48 and 96 weeks
Time Frame
96 weeks
Title
Modification of bone density and subcutaneous fat at 48 and 96 weeks
Time Frame
96 weeks
Title
Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks
Time Frame
96 weeks
Title
Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy
Time Frame
96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea De Luca, Prof
Organizational Affiliation
Catholic University of the Sacred Heart
Official's Role
Principal Investigator
Facility Information:
Facility Name
Catholic University of Sacred Heart
City
Rome
ZIP/Postal Code
00168
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

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