Clinical trial NCT01367210: Switch to Darunavir/r + Maraviroc Quaque Die in Patients With R5 Tropism by Viral DNA Genotyping (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
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HIV
AIDS
Highly Active AntiRetroviral Therapy
Simplification
Maraviroc
Darunavir
Treatment experienced
Tropism
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2011-06-07
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: 48 weeks
Secondary outcomes:
measure: 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
timeFrame: 96 weeks
measure: Time to virological failure at survival analysis
timeFrame: 48 weeks
measure: Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping)
timeFrame: 48 weeks
measure: Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks
timeFrame: 96 weeks
measure: Evolution of adherence and quality of life after 24, 48 and 96 weeks
timeFrame: 96 weeks
measure: Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks
timeFrame: 96 weeks
measure: Evolution of metabolic parameters at 96 weeks
timeFrame: 96 weeks
measure: Change of the results of neurocognitive tests at 48 and 96 weeks
timeFrame: 96 weeks
measure: Modification of bone density and subcutaneous fat at 48 and 96 weeks
timeFrame: 96 weeks
measure: Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks
timeFrame: 96 weeks
measure: Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Catholic University of Sacred Heart
Study officials:
affiliation: Catholic University of the Sacred Heart
name: Andrea De Luca, Prof
role: PRINCIPAL_INVESTIGATOR
References: