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

Phase 2

Completed

• Conditions: HIV Infections
• Interventions: Drug: efavirenz/emtricitabin/tenofovir; Drug: lopinavir/ritonavir

• Registration Number: NCT00946595
• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

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 Timeline

• Study First Submitted: 2009-07-24
• Study First Submitted QC: 2009-07-24
• Study First Posted: 2009-07-27
• Study Start: 2009-11
• Primary Completion: 2013-07
• Study Completion: 2014-01
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-23
• Last Update Posted: 2014-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 420

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
efavirenz/emtricitabin/tenofovir	efavirenz/emtricitabin/tenofovir	-
lopinavir/ritonavir	lopinavir/ritonavir	-

Primary Outcome Measures

Name	Time	Method
Proportion of patients without treatment failure at Week 96	Week 96

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Service des maladies infectieuses et tropicales Hopital Saint-Antoine; 🇫🇷 Paris, France