HIV Infection
Conditions
Keywords
HIV, AIDS, Highly Active AntiRetroviral Therapy, Simplification, Maraviroc, Darunavir, Treatment experienced, Tropism
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.
Interventions
DRUGMaraviroc, Darunavir/r
Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg
DRUGcurrent antiretroviral therapy with 3 drugs
To continue the assumption of previous HAART
Sponsors
Catholic University of the Sacred Heart
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Evolution of metabolic parameters at 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 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 |
| Time to virological failure at survival analysis | 48 weeks |
Countries
Italy
Outcome results
None listed