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Mulualem Mihret Gelaw,1 Ejigu Gebeye Zeleke,2 Mezgebu Silamsaw Asres,3 Mebratu Mitiku Reta3 1Felegehiwot Referral Hospital, Bahirdar, Ethiopia; 2Department of Epidemiology and Biostatistics, Institution of Public Health, University of Gondar, Gondar, Ethiopia; 3Department of Internal Medicine, School of Medicine, University of Gondar, Gondar, EthiopiaCorrespondence: Mebratu Mitiku Reta Email mebretann16@gmail.comBackground: Depression is the most common co-morbidity among perinatal women living with HIV. It affects client’s adherence to care and treatment, which results in increased viral load; further exposing women to opportunistic infections that reduce quality-of-life. A cumulative effect of these may increase mother-to-child transmission of HIV.Methods: An institution-based cross-sectional study was conducted among perinatal women living with HIV in Gondar town health facilities, Northwest Ethiopia from October 1– 30, 2018. A single population proportion formula was used to calculate the sample size. The sample was stratified and proportionally allocated to each health facility. Participants were chosen from each stratum independently using a simple random sampling technique. A total of 422 study participants were selected. The World Health Organization (WHO) 20-item self-reported questionnaire (SRQ-20) was used to measure perinatal depression among women living with HIV. Perceived stigma was measured using HIV stigma scale. Women were interviewed at the PMTCT clinic during follow-up care, and clinical variables were extracted from client chart. Bi-variable and multivariable logistic regression models were used to identify factors associated with perinatal depression. Variables having an odds ratio with 95% confidence interval and a P-value less than 0.05 were taken as significant variables associated with perinatal depression.Results: The prevalence of perinatal depression among women living with HIV was found to be 38.4% (95% CI=34.1– 43.1%). Fair and poor ART drug adherence (AOR=5.44; 95% CI= 2.81– 10.56%), the presence of comorbid illness (AOR=3.24; 95% CI: 1.83– 5.75), being on second line ART (AOR=2.97; 95% CI=1.08– 8.17), perceived stigma (AOR=3.61; 95% CI=2.11– 6.17), and suicidal ideation (AOR=3.89; 95% CI=1.28– 11.81) were factors associated with perinatal depression.Conclusion: The prevalence of perinatal depression among women living with HIV was found to be high. Adherence counseling needs to be strengthened; preventing first line treatment failure has to be encouraged; greater emphasis has to be given for those women on second line ART. Early identification and management of co-morbidity has to be considered. HIV positive perinatal women need counseling to reduce HIV-related perceived stigma.Keywords: perinatal women, HIV/AIDS, depression, Ethiopia