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

• Published in: AIDS research and therapy 2016-04, Vol.13 (17), p.17-17, Article 17
• Main Authors: de Castro, Nathalie, Braun, Joséphine, Charreau, Isabelle, Lafeuillade, Alain, Viard, Jean-Paul, Allavena, Clotilde, Aboulker, Jean-Pierre, Molina, Jean-Michel
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Alanine Transaminase - blood; Antiretroviral drugs; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - etiology; Complications and side effects; Dosage and administration; Drug Substitution - adverse effects; Drug therapy; Enfuvirtide; Enzymes; Female; HIV; HIV Envelope Protein gp41 - adverse effects; HIV Envelope Protein gp41 - therapeutic use; HIV Fusion Inhibitors - adverse effects; HIV Fusion Inhibitors - therapeutic use; HIV infection; HIV Infections - drug therapy; HIV Integrase Inhibitors - adverse effects; HIV Integrase Inhibitors - therapeutic use; Human immunodeficiency virus; Humans; Incidence; Life Sciences; Liver; Liver Function Tests; Male; Middle Aged; Peptide Fragments - adverse effects; Peptide Fragments - therapeutic use; Raltegravir; Raltegravir Potassium - adverse effects; Raltegravir Potassium - therapeutic use; Risk Factors
• ISSN: 1742-6405; 1742-6405
• DOI: 10.1186/s12981-016-0101-3

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. 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. 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