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

Purpose

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).

Condition	Intervention	Phase
HIV Infections	Drug: efavirenz/emtricitabin/tenofovir Drug: lopinavir/ritonavir	Phase 2 Phase 3


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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Tenofovir Efavirenz Ritonavir Lopinavir Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:

Proportion of patients without treatment failure at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at all time points during the trial [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: Yes ]
Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
Proportion of patients with plasma HIV-1 RNA below 400 cp/mL at all time points during the trial [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: Yes ]
Evolution of CD4 cell count between Week 0 and Week 96 [ Time Frame: Between Week 0 and Week 96 ] [ Designated as safety issue: No ]
Evaluation of treatment adherence [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: No ]
Evaluation of treatment tolerance [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: Yes ]
Number and type of new resistance mutations in case of two successive plasma HIV-1 RNA ≥ 400 cp/mL [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: Yes ]
Proportion of patients with loss of future drug options [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: No ]
Evaluation of quality of life assessments [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: No ]
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 [ Time Frame: Between Week 0 and Week 96 ] [ Designated as safety issue: No ]
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 [ Time Frame: Between Week 0 and Week 96 ] [ Designated as safety issue: Yes ]
Evolution of densitometric parameters between Week 0 and Week 96 in 80 patients [ Time Frame: Between Week 0 and Week 96 ] [ Designated as safety issue: Yes ]
Analysis of the determinants of the durability of the virological response [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: No ]
Assessment of pharmacokinetic and pharmacodynamic parameters in both groups if relevant [ Time Frame: From Week 0 to Week 96 ] [ Designated as safety issue: No ]


Estimated Enrollment:	420
Study Start Date:	November 2009
Study Completion Date:	January 2014
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: efavirenz/emtricitabin/tenofovir	Drug: efavirenz/emtricitabin/tenofovir 1x600/200/245 mg per day (one tablet) between W0 et W98 Other Name: Atripla
Experimental: lopinavir/ritonavir	Drug: lopinavir/ritonavir 4 x 200/50 mg (4 tablets) once a day between W0 and W98 Other Name: Kaletra

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00946595

Locations


France
Service des maladies infectieuses et tropicales Hopital Saint-Antoine
Paris, France, 72012

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Abbott

Gilead Sciences

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site


Responsible Party:	French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:	NCT00946595 History of Changes
Other Study ID Numbers:	2009-009776-13 ANRS 140 DREAM
Study First Received:	July 24, 2009
Last Updated:	June 23, 2014
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):


Undetectable HIV infections Monotherapy	Lopinavir/ritonavir Protease inhibitor Treatment experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Efavirenz Tenofovir Ritonavir Lopinavir Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors	Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers Anti-HIV Agents HIV Protease Inhibitors Protease Inhibitors Cytochrome P-450 CYP3A Inhibitors

HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Efavirenz
Tenofovir
Ritonavir
Lopinavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors
Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016

Evaluation of a Lopinavir/Ritonavir Monotherapy vs a Triple Therapy as Maintenance Regimens in HIV-1 Infected Patients (ANRS 140 DREAM)