Incidence and risk factors for liver enzymes elevations (LEE) in highly treatment-experienced patients switching from ENF (ENF) to RAL (RAL): sub-study of the ANRS-138 easier trial

Background: In the 48-weeks (W48) EASIER trial, 169 highly treatment-experienced patients well suppressed with ENF-based regimen were randomized to immediate or deferred (at W24) switch from ENF to RAL.
Methods: We assessed the incidence and risk factors for any new Grade2 or more LEE (ALT, alkaline phosphatase (ALP) and g-glutamyl transferase (gGT)). We performed a direct comparison between the two arms up to W24 and then an observational analysis including all patients receiving RAL up to W48.
Results: At baseline, all but one patients had a boosted-PI regimen with 29 (34%) and 37 patients (44%) on tipranavir/ritonavir (TPV/r) in the ENF and RAL arms, respectively. During the first 24 Weeks, 2 (2.4%) patients in ENF arm vs 6 (7.1%) in RAL arm experienced a Grade>2 ALT rise (p=0.28). In the observational analysis, 17 Grade>2 events occurred with an incidence of 14.6 events for 100-pts-years. In 9 patients TPV was replaced by another PI and RAL could be resumed in all patients.During the first 24 weeks there was no difference between the 2 arms regarding Grade>2 gGT or Grade>2 ALP rise. Overall, the incidence of Grade>2 gGT and Grade>2 ALP rises was 30.9 events for 100-pts-years and 5.2 events for 100-pts-years respectively in patients receiving RAL.When analyzing risk factors associated with a Grade>2 ALT rise during the comparative phase of the study there was a trend towards more events among patients receiving TPV/r vs no TPV/r (9% vs 2%, p=0.06). In the observational phase, TPV/r use was the only variable significantly associated with LEE (18.2% vs 4.9% for no use, p=0.006). Only one patient with LEE was HCV co-infected.
Conclusion: The incidence of LEE was quite high in these patients switching to a RAL-based regimen. RAL itself was not associated with LEE whereas TPV/r was significantly associated with an increased risk of LEE.

N. De Castro1, J. Braun2, I. Charreau2, A. Lafeuillade3, J.-P. Viard4, C. Allavena5, J.-P. Aboulker2, J.-M. Molina1, ANRS 138 study group
1AP-HP, Hôpital Saint-Louis, Infectious Diseases, Paris, France, 2INSERM SC10, Villejuif, France, 3Toulon Hospital, Immunology, Toulon, France, 4AP-HP, Hôpital Hôtel Dieu, Immunology, Paris, France, 5Nantes University Hospital, Infectious Diseases, Nantes, France