Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtide-based regimens: 48 week results of the randomized EASIER ANRS 138 trial.

OBJECTIVES: To assess the sustainable efficacy and safety of a switch from enfuvirtide to raltegravir in patients with multidrug-resistant HIV infection.

METHODS: One hundred and seventy patients with multidrug-resistant HIV infection and suppressed plasma HIV RNA levels < 400 copies/mL under an enfuvirtide-based regimen were randomized to maintain their regimen or to switch to a raltegravir-based regimen (immediate group) in a 48 week prospective, randomized, open-label trial. At week 24, patients in the maintenance arm also switched to raltegravir (deferred group). Baseline genotypic susceptibility scores (GSSs) were calculated using available historical resistance tests. Efficacy was assessed by the cumulative proportion of patients with virological failure, defined as a confirmed plasma HIV RNA ≥ 400 copies/mL up to week 48. The EASIER ANRS 138 trial is registered at ClinicalTrials.gov (NCT00454337).

RESULTS: At baseline, 86% of patients had plasma HIV RNA levels <50 copies/mL and 86% had a GSS ≥ 1. Through to week 48, in the on-treatment analysis, only one patient in the immediate group, with a GSS of 0, developed virological failure. At week 48, 90% of patients in both the immediate and deferred groups had plasma HIV-1 RNA levels <50 copies/mL. Median CD4 cell counts remained stable during follow-up. Of note, 12 of 66 (18.2%) patients receiving a regimen combining raltegravir and ritonavir-boosted tipranavir experienced alanine aminotransferase elevations, which led to a switch from tipranavir to darunavir in 8 cases, without discontinuation of raltegravir.

CONCLUSIONS: In well-suppressed patients with multidrug-resistant HIV infection, a switch from enfuvirtide to raltegravir is generally well tolerated and has sustained antiviral efficacy when combined with a potent background regimen.