Incidence and risk factors for liver enzyme elevation during 1 highly active antiretroviral therapy in HIV - HCV co - infected patients : 2 results from the Italian EPOKA - MASTER Cohort 3 4

1 2 Background: The risk of hepatotoxicity associated with different highly active 3 antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, 4 single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV5 HCV co-infected patients has not been fully assessed. 6 Methods: Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co7 infected patients who commenced a new HAART in the Italian MASTER database. 8 Patients were stratified into naïve and experienced to antiretroviral therapy before 9 starting the study regimens. Time to grade ≥III hepatotoxicity was the primary outcome. 10 Secondary outcome was time to grade IV hepatotoxicity. 11 Results: Incidence of grade ≥III hepatotoxicity was 17.71 per 100 patient-years (p-yr) 12 of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade 13 IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only 14 independent factors associated with shorter time to the event at proportional hazard 15 regression model were: previous liver transaminase elevations to grade >III, higher 16 baseline alanine amino-transferase values, and use of a non nucleoside reverse 17 transcriptase inhibitor based regimen. In the naive group, baseline aspartate 18 transaminase level was associated with the primary outcome. 19 Conclusions: Use of a single or multiple PI-based regimen was not associated with risk 20 of hepatotoxicity in either naïve or experienced patient groups. A cautious approach 21 with strict monitoring should be applied in HIV-HCV co-infected experienced patients 22 with previous liver transaminase elevations, higher baseline alanine amino-transferase 23