Clinical trial NCT00946595: Evaluation of a Lopinavir/Ritonavir Monotherapy vs a Triple Therapy as Maintenance Regimens in HIV-1 Infected Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infections
Keywords: Undetectable
HIV infections
Monotherapy
Lopinavir/ritonavir
Protease inhibitor
Treatment experienced
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Abbott
name: Gilead Sciences
First posted: 2009-07-27
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Proportion of patients without treatment failure at Week 96
timeFrame: Week 96
Secondary outcomes:
measure: Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at all time points during the trial
timeFrame: From Week 0 to Week 96
measure: Proportion of patients with plasma HIV-1 RNA below 50 cp/mL at Week 96
timeFrame: Week 96
measure: Proportion of patients with plasma HIV-1 RNA below 400 cp/mL at all time points during the trial
timeFrame: From Week 0 to Week 96
measure: Evolution of CD4 cell count between Week 0 and Week 96
timeFrame: Between Week 0 and Week 96
measure: Evaluation of treatment adherence
timeFrame: From Week 0 to Week 96
measure: Evaluation of treatment tolerance
timeFrame: From Week 0 to Week 96
measure: Number and type of new resistance mutations in case of two successive plasma HIV-1 RNA ≥ 400 cp/mL
timeFrame: From Week 0 to Week 96
measure: Proportion of patients with loss of future drug options
timeFrame: From Week 0 to Week 96
measure: Evaluation of quality of life assessments
timeFrame: From Week 0 to Week 96
measure: 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
timeFrame: Between Week 0 and Week 96
measure: 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
timeFrame: Between Week 0 and Week 96
measure: Evolution of densitometric parameters between Week 0 and Week 96 in 80 patients
timeFrame: Between Week 0 and Week 96
measure: Analysis of the determinants of the durability of the virological response
timeFrame: From Week 0 to Week 96
measure: Assessment of pharmacokinetic and pharmacodynamic parameters in both groups if relevant
timeFrame: From Week 0 to Week 96
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des maladies infectieuses et tropicales Hopital Saint-Antoine
Study officials:
References:
citation: Garay OU, Nishimwe ML, Bousmah MA, Janah A, Girard PM, Chene G, Moinot L, Sagaon-Teyssier L, Meynard JL, Spire B, Boyer S. Cost-Effectiveness Analysis of Lopinavir/Ritonavir Monotherapy Versus Standard Combination Antiretroviral Therapy in HIV-1 Infected Patients with Viral Suppression in France (ANRS 140 DREAM). Pharmacoecon Open. 2019 Dec;3(4):505-515. doi: 10.1007/s41669-019-0130-7.
citation: Lambert-Niclot S, Grude M, Meynard JL, Marcelin AG, Valantin MA, Flandre P, Izopet J, Moinot L, Bouteloup V, Calvez V, Katlama C, Girard PM, Morand-Joubert L. Ultrasensitive Human Immunodeficiency Virus Type 1 Viral Load as a Marker of Treatment Choice for Simplification Strategies. Clin Infect Dis. 2018 Nov 28;67(12):1883-1889. doi: 10.1093/cid/ciy382.