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BACKGROUND:HematologicalcomplicationssuchasZidovudine(ZDV) associated anemia are among the commonlyreported adverse drug reactions of Antiretroviral Therapy(ART).Little is known about ZDV associated anemia in developingcountries like Ethiopia.METHODS: Comparative retrospective cohort study was conductedat the ART Clinic of St. Paul Hospital Millennium Medical Collegefrom February 2011 to December 2012 to characterize anemiaamong HIV/AIDS patients initiated with ZDV and non-ZDVcontaining ART regimens. In each group, 197 HIV infected adultswho had complete medical records were included. Medical recordsof participants were reviewed using pre-tested data collectionformat. Data were analyzed using SPSS version 19 for windows.For all statistical significance tests, the cut-off value was P<0.05.RESULTS: Among ZDV group, anemia prevalence was 20.8 %(41/197), 33.5%(66 /197) and 13%(19/146) at baseline, six andtwelve months of ART follow-up, respectively.On the other hand innon-ZDV group, anemia was present among 44.2% (87/197), 18.3%(36/197) and 12.4% (25 /202) of participants at baseline, six andtwelve months of ART follow-up, respectively. After six months offollow-up, ZDV associated anemia was present among 32.7%(51/156) of the participants, and 43.1% of them were severe whileabout 45.2% were macrocytic type. Zidovudine group participantswere 3.34 times more likely to develop severe anemia than non-ZDV group, P< 0.001.CONCLUSION: The prevalence, severity and characteristics ofanemia were different between ZDV and non-ZDV groupparticipants at different follow-up periods of ART. Zidovudine hadsignificant contribution to severe anemia incidence after six monthsof ART; thus, hemoglobin level monitoring with red cell indices issuggested for improved detection of zidovudine associated anemia.