Abstract
HIV drug resistance (HIVDR) presents a significant challenge to antiretroviral therapy (ART) success, particularly in resource-limited settings like Ethiopia. This cross-sectional study investigated viral suppression rates and resistance patterns among patients on second-line ART across 28 Ethiopian health facilities. Blood samples collected from 586 participants were analyzed to measure CD4 count and viral load and assess HIVDR in patients experiencing virological failure (VF) (viral load ≥ 1000 copies/mL). Demographic and clinical data were analyzed using logistic regression to identify factors associated with VF. Results showed that 13.82% of participants experienced VF, with 67.57% of genotyped samples exhibiting at least one drug resistance mutation. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) was detected in 48.64%, 64.86%, and 18.92% of cases, respectively. Dual-class resistance was identified in 48.64% of patients, while triple-class resistance was detected in 18.92%. VF was more likely among students and those with CD4 counts below 200 cells/mm³, but less likely in patients on second-line treatment for 12 months or more. Our findings highlight a substantial HIVDR burden among patients on second-line ART with VF, emphasizing the need for comprehensive HIV care, including adherence support, regular viral load monitoring, and HIVDR testing.