Dolutegravir + Rilpivirine Switch Study (DORISS)

• Status: Withdrawn
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nantes University Hospital
• Treatments: Dolutegravir; Rilpivirine

Criteria

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.