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. (RADAR)

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.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV-1 Infection
• Intervention / Treatment: Drug: darunavir

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94275
    • Centre Hospitalier Universitaire de Bicêtre - Service de Médecine Interne et Maladies Tropicales
  • Paris, France, 75013
    • Groupe Hospitalier Pitié-Salpêtrière - Service des Maladies Infectieuses et Tropicales
  • Paris, France, 75013
    • Groupe Hospitalier Pitié-Salpêtrière - Service de Médecine Interne
  • Paris, France, 75015
    • Hôpital Necker Enfants Malades - Service des Maladies Infectieuses et Tropicales
  • Paris, France, 75020
    • Hôpital Tenon - Service des Maladies Infectieuses et Tropicales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darunavir/r	Drug: darunavir; darunavir/r 800/100 mg once daily by oral route, 48 weeks of treatment

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida
• Investigators: Study Director: Christine Katlama, MD, Groupe Hospitalier Pitie-Salpetriere; Principal Investigator: Jade Ghosn, MD, Centre Hsopitalier Universitaire de Bicêtre

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: February 20, 2009
• First Submitted That Met QC Criteria: February 20, 2009
• First Posted (Estimate): February 23, 2009

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 21, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Treatment Experienced
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Darunavir
• Other Study ID Numbers: CREPATS 001