Evaluation of a Dose Reduction of Darunavir (400 mg/d) in Virologically Suppressed HIV-1 Patients

Study Overview
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Brief Summary
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Phase II trial assessing the efficacy of a reduced dose strategy of darunavir to 400 mg/d in HIV-1 infected patients virologically suppressed under a once daily regimen including darunavir 800 mg/d and two nucleoside reverse transcriptase inhibitors (NRTI), to maintain the viral load lower than 50 copies / mL at 48 weeks of treatment.

Detailed Description
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Principal objective: To evaluate the proportion of subjects virologically suppressed at week 48 (viral load=VL ≤ 50 cp/mL) under a tri-therapy containing the darunavir at the dose of 400 mg/d. Secondary objectives: To evaluate between baseline and week 48: proportions of subjects: in virological failure (confirmed VL > 50 cp/mL) confirmed by a 2nd measure made between 2 to 4 weeks, with VL ≤ 50 cp/mL and between 20 and 50 cp/mL, emerging drug resistance if virological failure, CD4 cell count evolution, HIV DNA evolution, morphological and glucido-lipid parameters modifications, digestive treatment tolerance , adherence to treatment, overall cost of antiretroviral therapy, factors associated to virological failure including baseline and nadir CD4 cell count, darunavir plasma level, baseline HIV DNA viral load.

Official Title
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Phase II Trial Assessing the Efficacy of a Reduced Dose Strategy of Darunavir to 400 mg/d in HIV-1 Infected Patients Virologically Suppressed Under a Once Daily Regimen Including Darunavir 800 mg/d and Two Nucleoside Reverse Transcriptase Inhibitors (NRTI), to Maintain the Viral Load Lower Than 50 Copies / mL at 48 Weeks of Treatment

Conditions
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HIV INFECTION

Intervention / Treatment
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* Drug: Darunavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected adults, age ≥ 18 years, with a once-a-day ritonavir-boosted darunavir 800mg/j containing regimen plus 2 NRTI (≥ 6 months), virologically controlled (VL ≤ 50 cp/ml, ≥ 1 year, at least 2 VL spaced at least 3 months apart in the last 12 months) CD4 count ≥ 300/mm3 ≥ 6 months, virus sensible to darunavir and the used NRTI (pretreatment resistance genotypic test available) and with no history of virological failure (VL > 200 cp/mL after ≥ 6 months under PI and/or used NRTI), no current opportunistic infection, renal clearance ≥ 60 mL/min if tenofovir is used, transaminases (SGOT, SGPT) plasma levels < 2N, hemoglobin > 11 g/dL, platelets count > 150 000/mm3, negative pregnancy test in women with childbearing potential, informed written consent signed by both the investigator and the subject, national insurance scheme (article L1121-11 of the French Public Health code), no participation to any other clinical trial Exclusion Criteria: HIV-2 infection, current antiretroviral therapy different from a once-a-day ritonavir-boosted darunavir 800mg/j containing regimen plus 2 NRTI, virus genotypically resistant to darunavir and the used NRTIs, history of virological failure (VL > 200 cp/mL after ≥ 6 months under PI and/or used NRTI), irregular follow-up and/or history of lack of adherence to ART ≤ 12 months, current pregnancy, current opportunistic infection, associated treatment containing one or more drugs interacting with hepatic cytochromes, any addictive behaviors (alcohol consumption, drugs …) likely to jeopardize the safety of the treatment and / or patient compliance and adherence to the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darunavir 400mg/d<br>Tri-therapy containing Darunavir at dose of 400 mg/d. | Drug: Darunavir<br>* to assess efficacy of a reduced dose strategy of darunavir to 400 mg/d in HIV-1 infected patients virologically suppressed under a once daily regimen including darunavir 800 mg/d and two nucleoside reverse transcriptase inhibitors (NRTI), to maintain the viral load lower than 50 copies / mL at 48 weeks of treatment.<br>* Other names: Prezista;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with therapeutic success, defined as no virological failure | Virological failure is defined as confirmed VL > 50 cp/mL and no change of the strategy | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of patients with virological failure (confirmed VL > 50 cp/ml) |  | Week 48 | 
| Proportions of patients with VL < 50 cp/ml |  | Week 12, Week 24, Week 36, Week 48 | 
| Proportions of patients with VL between 20 and 50 cp/ml |  | Week 12, Week 24, Week 36, Week 48 | 
| Change from baseline in blood CD4 cell count at week 12, week 24, week 36 and week 48 |  | Week 12, Week 24, Week 36, Week 48 | 
| Change from baseline in blood HIV DNA at week 48 |  | Week 48 | 
| Emerging drug resistance if virological failure |  | Week 48 | 
| Treatment adherence |  | Week 48 | 
| Change from baseline in blood lipids at week 24 and week 48 |  | Week 24 and Week 48 | 
| Change from baseline in glucose at week 24 and week 48 |  | Week 24 and Week 48 | 
| Treatment Digestive tolerance |  | Week 48 |