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

Phase 4

Terminated

• Conditions: HIV Infection
• Interventions: Drug: Maraviroc, Darunavir/r; Drug: current antiretroviral therapy with 3 drugs

• Registration Number: NCT01367210
• Lead Sponsor: Catholic University of the Sacred Heart

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-06-03
• Study First Submitted QC: 2011-06-03
• Study First Posted: 2011-06-07
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-05
• Last Update Posted: 2016-02-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 165

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MARAVIROC, DARUNAVIR/r	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
current ART with 3 drugs	current antiretroviral therapy with 3 drugs	Patients on HAART with three drugs and HIV RNA below 50 copies/mL

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 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
Evolution of adherence and quality of life after 24, 48 and 96 weeks	96 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 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
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

Trial Locations

Locations (1)

Catholic University of Sacred Heart; 🇮🇹 Rome, Italy