IntroductionVirological suppression for persons living with HIV (PLHIV) on antiretroviral therapy (ART) reached 85% at the end of 2018, still falling short of the UNAIDS target of 95%. In Ethiopia, there were studies on treatment failure focusing on viral suppression and immunological failure of ART users, but none of them have addressed virological failure for second-line regimens.ObjectiveThis study was aimed to estimate the incidence and predictors of virological failure among HIV patients who were switched to second-line ART at the selected public hospitals in Addis Ababa.MethodsAn institutional-based retrospective follow-up study was conducted from September 2018 to January 2021 at public hospitals in Addis Ababa. The sample size was determined by using the Schoenfeld formula. Data entry were done by Epi Data version-4.6.0.0 and exported to R-software version-4.1.0 for analysis. Kaplan–Meier methods were used to compare the survival estimates. Cox proportional hazard model was used to identify predictors of virological failure and model adequacy was checked by using the Cox–Snell residuals plot.ResultsOverall 44 (12.22%) HIV/AIDS patients developed virological failure with incidence density of 3.57/1000 Person-Month (PM) with 95% CI of [2.65–4.79]. Age >45 years (AHR=0.36, 95% CI: 0.12–0.99), CD4 count <100cell/mm3 (AHR=3.02, 95% CI: 1.17–7.78), TB co-infection (AHR=2.48, 95% CI: 1.10–6.33), ATV/r-based second-line regimen (AHR=0.27, 95% CI: 0.11–0.70), and poor adherence at the start of second-line ART (AHR=6.18, 95% CI: 1.93–19.76) were the significant predictors of virological failure.ConclusionA high incidence of virological failure was noticed. The rate of virological failure was higher for patients who had poor ART adherence, small CD4count, and TB co-infection. Therefore, targeted HIV care interventions shall be provided to young ages and efforts stepped up to improve adherence to ART, which helps to increase immunity and suppress viral replication. In addition, prevention and early detection of TB co-infection are crucial to the patients.