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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 420
- Locations
- 1
- Primary Endpoint
- Proportion of patients without treatment failure at Week 96
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/mm
- •Participation in another clinical trial interfering with the study drug assignment in DREAM
- •Subject under legal guardianship or incapacitation
Arms & Interventions
efavirenz/emtricitabin/tenofovir
Intervention: efavirenz/emtricitabin/tenofovir (Drug)
lopinavir/ritonavir
Intervention: lopinavir/ritonavir (Drug)
Outcomes
Primary Outcomes
Proportion of patients without treatment failure at Week 96
Time Frame: Week 96
Secondary Outcomes
- 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)
- 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)