Incidence and risk factors for liver enzymes elevations in highly treatment-experienced patients switching from enfuvirtide to raltegravir: a sub-study of the ANRS-138 EASIER trial

Nathalie de Castro, Joséphine Braun, Isabelle Charreau, Alain Lafeuillade, Jean-Paul Viard, Clotilde Allavena, Jean-Pierre Aboulker, Jean-Michel Molina, EASIER ANRS 138 study group, Nathalie de Castro, Joséphine Braun, Isabelle Charreau, Alain Lafeuillade, Jean-Paul Viard, Clotilde Allavena, Jean-Pierre Aboulker, Jean-Michel Molina, EASIER ANRS 138 study group

Abstract

Background: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm.

Methods: We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses.

Results: During the first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4 %) presented with ALT elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21). Grade 2 or more γGT and ALP elevations were seen in 18 and 11 % (p = 0.35), and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The 48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5 per 100-pts-years for γ-GT and 4.5 per 100-pts-years for ALP, respectively. In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % CI [1.20-11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % CI [2.67-39.6], p < 10(-3)) were significantly associated with a grade 2 or more ALT elevation during follow-up.

Conclusion: The incidence of LEE was relatively high in these highly treatment-experienced patients switching to a RAL-based regimen. Both tipranavir/ritonavir use and high baseline ALT levels were associated with an increased risk of ALT.

Trial registration: ClinicalTrials.gov identifier: NCT00454337.

Keywords: Liver enzymes; Raltegravir; Tipranavir; Transaminases.

Figures

Fig. 1
Fig. 1
Kaplan-Meier survival probability without grade 2 or more ALT elevation according to the use of tipranavir (TPV) in baseline regimen (BR)

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Source: PubMed

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