Incidence and risk factors for liver enzyme elevation during antiretroviral therapy in HIV/HCV coinfected patients RUNNING HEAD: Hepatotoxicity in HIV/HCV coinfection

Background: The risk of hepatotoxicity associated with different HAART regimens (multiple-PI, single-PI or NNRTI-based) in HCV co-infected patients has not been fully assessed. Methods: Retrospective analysis of a prospective cohort of 1,038 HIV/HCV coinfected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve (N) and experienced (E) to antiretroviral therapy. Time-tograde ≥III hepatotoxicity was the primary outcome. Secondary analyses were conducted using time-to-grade IV hepatotoxicity. Results: Incidence of grade ≥III hepatotoxicity was 17.71% per patient-year (p-yr) of follow up in N group and 8.22% per p-yr in E group (grade IV: 4.13% per p-yr and 1.08% per p-yr, respectively). The only factors significantly associated with time-tograde ≥III event among N patients were baseline AST level and slope of CD4+ cell recovery. By contrast, baseline ALT, history of previous hepatotoxicity and use of a NNRTI-based regimen were independently associated with time to event among E patients. Conclusions: Use of a single or multiple PI-based regimen was not associated with risk of hepatotoxicity in either N or E groups. A cautious approach with strict monitoring should be applied in coinfected E patients with previous hepatotoxicity, higher baseline ALT values and who receive NNRTI containing regimens.