Study of Protease Inhibitor Regimen Switch in HIV-1 Infected Patients With Undetectable Viral Load to Prove the Non-inferiority of Once Daily Dose Regimen Versus the Current Twice Daily Regimen to Maintain the Viral Load Under the Limit of Detection.

Study Overview
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Brief Summary
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Darunavir boosted with ritonavir (darunavir/r) is a powerful protease inhibitor, able to reduce the viral load in patients infected with multi-resistant HIV strains; In vitro and in vivo studies have shown that the induction of resistance mutations in the protease gene is much more difficult with the association darunavir/r compared to the other ritonavir-boosted protease inhibitors (PI/r), testifying of a significantly higher genetic barrier to resistance. Moreover, the tolerance to darunavir is good, and the pharmacologic profile of this molecule allows a once daily administration with a 800/100 mg dose in patients infected with a wild HIV strain or with a slightly resistant to darunavir/r strain. Thus, we propose to evaluate the efficacy of the darunavir/r association once daily as a substitute to a protease inhibitor regimen administered twice daily in patients with undetectable viral load receiving a tritherapy including a protease inhibitor administered twice daily.

Official Title
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Non-comparative, Opened Study, Evaluating in HIV-1 Infected Patients With Undetectable Viral Load, Treated by an Antiretroviral Combination Including a Protease Inhibitor Boosted With Ritonavir and Administered by Oral Route Twice a Day, the Substitutability of the Current Protease Inhibitor Regimen by the Association Darunavir/Ritonavir 800/100 mg Once a Day to Maintain the Viral Load Under the 50 Copies/ml Limit of Detection After 24 Weeks of Treatment.

Conditions
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HIV-1 Infection, HIV Infections

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 patients Treatment with an association of 3 molecules including two Nucleotidic Reverse Trasncriptase Inhibitors and a ritonavir-boosted protease inhibitor BID, unchanged for at least one month At least two documented undetectable viral loads (under 50 copies/ml) within the last 3 months Naiive from darunavir Free from any opportunistic infection Creatinin < 3N ASAT & ALAT < 5N Haemoglobin > 7 g/dl Platelets > 50 000/mm3 Negative pregnancy test for women of childbearing potential and use of a mechanic contraceptive during sexual relationships Signed informed consent Exclusion Criteria: HIV-2 infected patients Treatment different from the association described in the inclusion criteria (2 NRTIs + 1 PI/r BID) Patients with a documented problem of treatment compliance within the last 12 months Ongoing active treatment against any opportunistic infection or tuberculosis Any critic concomitant condition (alcohol consumption, fatigue) that may jeopardize treatment compliance and/olr tolerance, and interfere with the protocol compliance Any concomitant treatment that may potentialize or inhibit hepatic cyotchrome-based enzymes Patient already treated with darunavir Patient treated with tipranavir, enfuvirtide, raltegravir, etravirine, and/or maraviroc

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/r<br> | Drug: darunavir<br>* darunavir/r 800/100 mg once daily by oral route, 48 weeks of treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable viral load ( < 50 copies/ml) |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable viral load under 50 copies/ml |  | All visits | 
| Proportion of patients in the situation of virologic failure defined as a viral load higher than 50 copies/ml confirmed with a second examen at least two weeks later. |  | All visits | 
| CD4 lymphocytes count and evolution |  | All visits | 
| Lipids balance evolution |  | All visits | 
| Treatment tolerance |  | All visits | 
| Measure of the darunavir/r concentrations variability and correlation with the potential adverse events and/or virologic failures. |  | All visits | 
| Spermatic viral load (sub-study concerning 15 patients) |  | Day 0 and Week 48 | 
| Pharmacologic sub-studies |  | All visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced