Objective The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). Methods Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. Results Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person‐years (7.8 per 100 person‐years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person‐years). There was no difference between patients from high‐ and low‐income countries [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P=0.040], a lower CD4 count (≥51 cells/μL vs. ≤50 cells/μL; adjusted HR 0.61, P=0.022) and a higher HIV viral load (≥400 HIV‐1 RNA copies/mL vs. <400 copies/mL; adjusted HR 2.69, P<0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low‐income countries, patients from high‐income countries were more likely to change two or more drugs (67%vs. 49%; P=0.009) and to change to a protease‐inhibitor‐containing regimen (48%vs. 16%; P<0.001). Conclusions In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second‐line treatment. There is a need to scale up the availability of second‐line regimens and virological monitoring in this region.