Clinical trial NCT00849160: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
HIV Infections
Keywords: Treatment Experienced
Lead sponsor: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida
Sponsor class: OTHER
First posted: 2009-02-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Undetectable viral load ( < 50 copies/ml)
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of patients with undetectable viral load under 50 copies/ml
timeFrame: All visits
measure: 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.
timeFrame: All visits
measure: CD4 lymphocytes count and evolution
timeFrame: All visits
measure: Lipids balance evolution
timeFrame: All visits
measure: Treatment tolerance
timeFrame: All visits
measure: Measure of the darunavir/r concentrations variability and correlation with the potential adverse events and/or virologic failures.
timeFrame: All visits
measure: Spermatic viral load (sub-study concerning 15 patients)
timeFrame: Day 0 and Week 48
measure: Pharmacologic sub-studies
timeFrame: All visits
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: Centre Hospitalier Universitaire de Bicêtre - Service de Médecine Interne et Maladies Tropicales
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière - Service de Médecine Interne
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: Hôpital Necker Enfants Malades - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: Hôpital Tenon - Service des Maladies Infectieuses et Tropicales
Study officials:
affiliation: Centre Hsopitalier Universitaire de Bicêtre
name: Jade Ghosn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Hospitalier Pitié-Salpêtrière
name: Christine Katlama, MD
role: STUDY_DIRECTOR
References: