BackgroundThe number of patients using second-line antiretroviral therapy (ART) has increased over time. In Ethiopia, 1.5% of HIV infected patients on ART are using a second-line regimen and little is known about its effect in this setting.ObjectiveTo estimate the rate and predictors of treatment failure on second-line ART among adults living with HIV in northwest Ethiopia.SettingAn institution-based retrospective follow-up study was conducted at three tertiary hospitals in northwest Ethiopia from March to May 2015.Participants356 adult patients participated and 198 (55.6%) were males. Individuals who were on second-line ART for at least 6 months of treatment were included and the data were collected by reviewing their records.Primary outcome measureThe primary outcome was treatment failure defined as immunological failure, clinical failure, death, or lost to follow-up. To assess our outcome, we used the definitions of the WHO 2010 guideline.ResultThe mean±SD age of participants at switch was 36±8.9 years. The incidence rate of failure was 61.7/1000 person years. The probability of failure at the end of 12 and 24 months were 5.6% and 13.6%, respectively. Out of 67 total failures, 42 (62.7%) occurred in the first 2 years. The significant predictors of failure were found to be: WHO clinical stage IV at switch (adjusted HR (AHR) 2.1, 95% CI 1.1 to 4.1); CD4 count <100 cells/mm3 at switch (AHR 2.0, 95% CI 1.2 to 3.5); and weight change (AHR 0.92, 95% CI 0.88 to 0.95).ConclusionsThe rate of treatment failure was highest during the first 2 years of treatment. WHO clinical stage, CD4 count at switch, and change in weight were found to be predictors of treatment failure.