HAART-treated, HIV Infection, Virologically Controlled
Conditions
Keywords
Dolutegravir, Rilpivirine, PI- and NRTI- sparing ART regimen, switch study
Brief summary
The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent). The main secondary objectives are the following: * % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48 * % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48 * % of virological failure defined by two consecutive plasma viral load \> 50 copies/mL * Profile of genotypic resistance in case of virological failure. The trial will be conducted according to the design below, in 3 steps: * Step 1: enrollment of 80 patients (40 in each arm) * Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed. * Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly \> 70%, which translates in a maximum of 6 virologic failures.
Interventions
DRUGArm 1 (intervention)
Dolutegravir 50 mg/j + Rilpivirine 25 mg/j qd orally (intake during meal)
DRUGArm 2 (control)
Continuation of existing HAART at the time of randomization
Sponsors
Nantes University Hospital
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
* Age ≥ 18 years * HIV-1 infection * Treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, or 1 NNRTI, or INI), unchanged for \> 6 months, Intra-class substitution within past 6 months is not considered as a treatment change. * Plasma HIV-RNA ≤ 50 copies/mL for \> 2 years * CD4 cell count \> 350/mm3 for \> 6 months * No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen * No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D. * No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S * Negative HBs Ag * Informed consent form signed by patient and investigator * A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study * Patient covered with health insurance * Effective contraception
Exclusion criteria
* HIV-2 infection * Dialysis or severe renal failure (creatinine clearance \< 30 ml/min) * History of decompensated liver disease * History of HIV-associated neurocognitive disorders * AST or ALT \> 5 x ULN * Positive HBc Ac and negative HBs Ac * Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug * Current pregnancy or breastfeeding * Patient involved in another research that precludes enrolment in another trial * Patient under guardianship, or deprived of liberty by a court or administrative decision.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16) | Week 16 |
| Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks | Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL | Week 48 | — |
| Measure of the profile of genotypic resistance in plasma in case of virologic failure | Week 48 | — |
| Percentage of patients who discontinued or changed the strategy of the study | Week 48 | — |
| Measure of the HIV-DNA between day 0 and week 48 | W48 | Evolution of the HIV-DNA between Day 0 and week 48 |
| Measure of CD4 lymphocytes at week 24 compared to day 0 | Week 24 | Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0 |
| Measure of CD4 lymphocytes at Week 48 compared to Day 0 | Week 48 | Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0 |
| Number of patients with adverse events of grade 2 to 4 | Week 48 | Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events |
| Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0 | Week 24 | Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0 |
| Measure of changes in serum lipid parameters at week 48 to Day 0 | Week 48 | Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0 |
| Measure of changes in fat mass distribution at week 24 compared to Day 0 | Week 24 | Changes in fat mass distribution at Week 24 compared to Day 0 |
| Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48 | Week 48 | — |
| Measure of adherence to treatment at Week 24 compared to Day 0 | Week 24 | Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire |
| Measure of adherence to treatment at Week 48 compared to Day 0 | Week 48 | Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire |
| Measure of patient satisfaction for their treatment at Day 0 | Day 0 | Assessment of patient satisfaction for their treatment at D0 by questionnaire |
| Measure of patient satisfaction for their treatment at Week 24 | Week 24 | Assessment of patient satisfaction for their treatment at Week 24 by questionnaire |
| Measure of patient satisfaction for their treatment at Week 48 | Week 48 | Assessment of patient satisfaction for their treatment at Week 48 by questionnaire |
| Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 . | Week 24 | Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 . |
| Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 . | Week 48 | Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 . |
| Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4 | Week 4 | Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4 |
| Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24 | Week 24 | Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24 |
| Measure of changes in fat mass distribution at Week 48 compared to Day 0 | Week 48 | Changes in fat mass distribution at Week 48 compared to Day 0 |
| Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48 | Week 48 | — |
Countries
France
Outcome results
None listed