HIV Infections
Conditions
Keywords
Undetectable, HIV infections, Monotherapy, Lopinavir/ritonavir, Protease inhibitor, Treatment experienced
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.
Interventions
DRUGefavirenz/emtricitabin/tenofovir
1x600/200/245 mg per day (one tablet) between W0 et W98
DRUGlopinavir/ritonavir
4 x 200/50 mg (4 tablets) once a day between W0 and W98
Sponsors
Abbott
Gilead Sciences
French National Agency for Research on AIDS and Viral Hepatitis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/mm3. * Participation in another clinical trial interfering with the study drug assignment in DREAM * Subject under legal guardianship or incapacitation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients without treatment failure at Week 96 | Week 96 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 plasma HIV-1 RNA below 400 cp/mL at all time points during the trial | 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 loss of future drug options | From Week 0 to Week 96 |
Countries
France
Outcome results
None listed