Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1 infected patients: final results of the randomized ANRS 138 trial (EASIER)

Background: Among patients with multidrug-resistant HIV infection, enfuvirtide-based regimens (EBR) can durably suppress viral replication but long-term use is inconvenient. We report here the final 48 results of a trial assessing the efficacy and safety of a switch from enfuvirtide to raltegravir within a fully suppressive regimen.
Methods: 170 pts with triple-class resistant HIV-1 infection and plasma HIV RNA < 400 cp/mL under EBR, were randomized 1:1 to either maintenance of EBR or switch to raltegravir. At week 24, pts in the EBR arm were offered to switch to raltegravir. The primary endpoint was the proportion of pts with virologic failure (VF), defined as confirmed plasma HIV RNA ≥ 400 cp/mL.
Results: At baseline 85% of pts were male, median age: 48 years, median CD4 count: 393 cells/mm3, 86% had HIV-1 RNA < 50 cp/mL. Median duration of EBR was 2.3 years. Through W24, there was one VF per arm in the ITT analysis (failure rate of 1.2%, delta: 0.01%; 95% CI: ‑6.7; +6.8), and only one VF in the raltegravir arm in the on-treatment analysis (delta: 1.22%; 95% CI: ‑5.6; +8.1) supporting non-inferiority of the raltegravir arm. All pts in the EBR arm switched to raltegravir at W24, with no subsequent VF in any arm up to week 48. 90% of pts in both arms had plasma HIV-1 RNA < 50 cp/mL at week 48. No significant CD4 changes occurred in either arm through W48. During the 24-48 weeks period, incidence of grade 3 to 4 adverse events and laboratory abnormalities were similar to those observed up to week-24 (7% and 12%, respectively).
Conclusion: In patients with multidrug-resistant HIV-infection receiving a suppressive antiretroviral regimen, a switch to raltegravir was safe, well tolerated and virologically non inferior to the maintenance of enfuvirtide.

N. De Castro1, J. Braun2, I. Charreau2, P. De Truchis3, F. Jeanblanc4, R. Verdon5, L. Slama6, J.-L. Meynard7, J.-P. Aboulker2, J.-M. Molina1,8, ANRS 138 Easier
1AP-HP Saint-Louis Hospital, Infectious Diseases, Paris, France, 2INSERM SC10, Villejuif, France, 3APH-HP Raymond Poincaré Hospital, Garches, France, 4Edouard Herriot Hospital, Lyon, France, 5Côte de Nacre Hospital, Caen, France, 6AP-HP Tenon Hospital, Paris, France, 7AP-HP Saint-Antoine Hospital, Paris, France, 8Paris 7 University, Paris, France