Background: The inclusion of protease inhibitors (PIs) in therapeutic regimens has a significantrnimpact on the success of the treatment; these classes have been associated with liver-related injuryrnrnin some individuals. Rates of hepatotoxicity from registration trials of various PIs havernranged from 1% to 9.5%, of which few patients had serious liver-related outcomes. rnObjective: To evaluate the incidence, severity, patterns, time dependent and risk factors of PIsrnbased anti-retroviral regimens induced liver injury. rnMethods: An observational cohort prospective study was conducted at anti-retroviral treatmentrnclinic of Zewditu memorial hospital. All patients that were HIV positive and candidate for PIrnbased regimens, and fulfilling other eligibility criteria were included in the study. The study wasrnconducted from March 1, 2018 to December 30, 2018 (including follow up period for total of 6rnmonths). rnResults: Out of 142 study participants, overall, liver injury of any grade was observed in 25rn(17.6%) participants. From 35 PI based naÃ¯ve participants, 3 patients developed liver injury duringrnthernstudyrnperiod.rnMajorityrnofrnthernparticipantsrn21rn(84%)rndevelopedrncholestaticrnpatternrnofrnliverrnrninjury.rnOverallrnincidencernofrngradern1,rn2rnandrn3rnwerern16rn(64%),rn6rn(24%)rnandrn3rn(12%)rnrespectively.rnrnThernrnincidence of liver injury was high (57.1%; 4/7) within 25-48 weeks from the starting PIrnbased regimens. Cotrimoxazole prophylactic therapy and previous first line on AZT/3TC/NVPrnwere significantly associated with liver injury. rnConclusion: Overall, liver injury of any grade was observed in 25 (17.6%) participants whilernonly 3 (12%) participants developed grade-3 liver injury. None of the participants developedrngrade-4 liver injury and no liver related death was reported during the study period. rnRecommendation: Regular follow up of liver function tests is important to monitor liver toxicitiesrninrnHIVrnpositivernpatients,rnparticularlyrnwithrnPIs-basedrnregimen.rnFurtherrnstudyrnneedrntornbernconductedrnwithrnlargernsamplernsizernandrnlongrntermrnfollowrnuprntornidentifyrnthernmechanismrnandrnriskrnfactorsrnrnassociatedrnwithrnPIs.