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

HIV Infection Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01367210
• Other study ID #: 2010-023316-13
• Status: Terminated
• Phase: Phase 4
• First received: June 3, 2011
• Last updated: February 5, 2016
• Start date: June 2011
• Est. completion date: June 2015

Study information

• Verified date: February 2016
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 165
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• Maraviroc, Darunavir/r
Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg
• current antiretroviral therapy with 3 drugs
To continue the assumption of previous HAART

Locations

Country	Name	City	State
Italy	Catholic University of Sacred Heart	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Time to virological failure at survival analysis		48 weeks	No
Secondary	Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping)		48 weeks	No
Secondary	Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks		96 weeks	No
Secondary	Evolution of adherence and quality of life after 24, 48 and 96 weeks		96 weeks	Yes
Secondary	Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks		96 weeks	No
Secondary	Evolution of metabolic parameters at 96 weeks		96 weeks	Yes
Secondary	Change of the results of neurocognitive tests at 48 and 96 weeks		96 weeks	Yes
Secondary	Modification of bone density and subcutaneous fat at 48 and 96 weeks		96 weeks	Yes
Secondary	Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks		96 weeks	Yes
Secondary	Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy		96 weeks	No