Evaluation of a Lopinavir/Ritonavir Monotherapy vs a Triple Therapy as Maintenance Regimens in HIV-1 Infected Patients

Study Overview
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Brief Summary
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A 2-year multicenter, phase II/III, randomized active-controlled trial to evaluate the efficacy and tolerance of two maintenance strategies in HIV-1 infected patients with HIV RNA below 50 copies/mL : a monotherapy with lopinavir/ritonavir or a single-tablet triple therapy (EFV/FTC/TDF).

Detailed Description
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Today, one of the challenges of HIV treatment is to overcome side effects and toxicity of long term antiretroviral therapy. A promising approach may be the simplification of treatment maintenance strategies, sparing certain antiretroviral drug classes. This is a two-year prospective phase II/III, multicenter randomized trial to evaluate the efficacy and tolerance of a lopinavir/ritonavir monotherapy as a maintenance regimen in HIV-infected adults. Enrolled patients must have had stable antiretroviral treatment and HIV-1 RNA below 50 cp/mL over the previous 12 months, and no prior treatment failure. Provided informed consent, 420 patients are randomized in a 1:1 ratio to two open-label treatment groups and receive either lopinavir/r 800/200mg per day or EFV/FTC/TDF 600/200/245 mg per day (fixed dose combination). The main objective is to assess treatment efficacy and tolerance after 2 years. In 80 patients, repeated DEXA measurements are performed during the trial in order to evaluate changes in bone mineral density and in body composition.

Official Title
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A Study Comparing Efficacy and Tolerance of Two Maintenance Strategies : a Monotherapy With Lopinavir/Ritonavir or a Single-tablet Triple Therapy by Efavirenz/Emtricitabin/Tenofovir in HIV-1 Infected Patients With HIV RNA Below 50 cp/mL

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: efavirenz/emtricitabin/tenofovir
* Drug: lopinavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV-1 infection Stable antiretroviral treatment over 6 months HIV-1 RNA < 50 cp/mL for at least 12 months Lymphocytes CD4+ > 200/mm3 Lymphocytes CD4+ nadir > 100/mm3 Absence of prior treatment failure (defined by two successive HIV-1 RNA ≥ 50 cp/mL under NNRTI or PI treatment) Absence of documentation of a mutation conferring NRTI or NNRTI resistance or a primary mutation in the protease gene Written informed consent Patient affiliated to a social security scheme Exclusion Criteria: Woman of child bearing potential without efficient contraception Pregnant or breastfeeding woman HBV infection (HbS Ag+) HBC infection requiring specific treatment during the trial Liver cirrhosis Child-Pugh C HIV-1/HIV-2 Co-infection or isolated HIV-2 infection Ongoing interleukin or interferon treatment Co-administration of contraindicated treatments Hypersensibility to efavirenz or lopinavir/r Absolute neutrophil count < 750/mm3, hemoglobin < 8g/dL, platelets < 60.000/mm3, creatinine clearance < 50 mL/min, ASAT, ALAT, lipase, alkaline phosphatase or total bilirubin > 3 ULN, CD4 nadir < 100/mm3. Participation in another clinical trial interfering with the study drug assignment in DREAM Subject under legal guardianship or incapacitation

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: efavirenz/emtricitabin/tenofovir<br> | Drug: efavirenz/emtricitabin/tenofovir<br>* 1x600/200/245 mg per day (one tablet) between W0 et W98<br>* Other names: Atripla;|
| Experimental: lopinavir/ritonavir<br> | Drug: lopinavir/ritonavir<br>* 4 x 200/50 mg (4 tablets) once a day between W0 and W98<br>* Other names: Kaletra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients without treatment failure at Week 96 |  | Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at all time points during the trial |  | From Week 0 to Week 96 | 
| Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at Week 96 |  | Week 96 | 
| Proportion of patients with plasma HIV-1 RNA below 400 cp/mL at all time points during the trial |  | From Week 0 to Week 96 | 
| Evolution of CD4 cell count between Week 0 and Week 96 |  | Between Week 0 and Week 96 | 
| Evaluation of treatment adherence |  | From Week 0 to Week 96 | 
| Evaluation of treatment tolerance |  | From Week 0 to Week 96 | 
| Number and type of new resistance mutations in case of two successive plasma HIV-1 RNA ≥ 400 cp/mL |  | From Week 0 to Week 96 | 
| Proportion of patients with loss of future drug options |  | From Week 0 to Week 96 | 
| Evaluation of quality of life assessments |  | From Week 0 to Week 96 | 
| Prevalence of acquired impairment in cognitive functioning, involving at least two ability domains, without interference in daily functioning or functioning complaint between Week 0 and Week 96 |  | Between Week 0 and Week 96 | 
| Prevalence of acquired impairment in cognitive functioning, involving at least two ability domains, with interference in daily functioning or functioning complaint between Week 0 and Week 96 |  | Between Week 0 and Week 96 | 
| Evolution of densitometric parameters between Week 0 and Week 96 in 80 patients |  | Between Week 0 and Week 96 | 
| Analysis of the determinants of the durability of the virological response |  | From Week 0 to Week 96 | 
| Assessment of pharmacokinetic and pharmacodynamic parameters in both groups if relevant |  | From Week 0 to Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Undetectable, HIV infections, Monotherapy, Lopinavir/ritonavir, Protease inhibitor, Treatment experienced