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

HIV Infections Clinical Trial

— ANRS 140 DREAM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00946595
• Other study ID #: 2009-009776-13
• Secondary ID: ANRS 140 DREAM
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 24, 2009
• Last updated: June 23, 2014
• Start date: November 2009
• Est. completion date: January 2014

Study information

• Verified date: June 2014
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: January 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• efavirenz/emtricitabin/tenofovir
1x600/200/245 mg per day (one tablet) between W0 et W98
• lopinavir/ritonavir
4 x 200/50 mg (4 tablets) once a day between W0 and W98

Locations

Country	Name	City	State
France	Service des maladies infectieuses et tropicales Hopital Saint-Antoine	Paris

Sponsors (3)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Abbott, Gilead Sciences

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients without treatment failure at Week 96		Week 96	Yes
Secondary	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	Yes
Secondary	Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at Week 96		Week 96	Yes
Secondary	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	Yes
Secondary	Evolution of CD4 cell count between Week 0 and Week 96		Between Week 0 and Week 96	No
Secondary	Evaluation of treatment adherence		From Week 0 to Week 96	No
Secondary	Evaluation of treatment tolerance		From Week 0 to Week 96	Yes
Secondary	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	Yes
Secondary	Proportion of patients with loss of future drug options		From Week 0 to Week 96	No
Secondary	Evaluation of quality of life assessments		From Week 0 to Week 96	No
Secondary	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	No
Secondary	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	Yes
Secondary	Evolution of densitometric parameters between Week 0 and Week 96 in 80 patients		Between Week 0 and Week 96	Yes
Secondary	Analysis of the determinants of the durability of the virological response		From Week 0 to Week 96	No
Secondary	Assessment of pharmacokinetic and pharmacodynamic parameters in both groups if relevant		From Week 0 to Week 96	No

External Links

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