Objective To evaluate the long-term efficacy of antiretroviral therapy and drug resistance among human immunodeficiency virus-1(HIV-1)-infected children in Yunnan.Methods In this retrospective study,CD4+T cell counts,HIV viral loads and genetic drug resistance results were obtained from HIV-1-infected children who were treated with antiretroviral treatment between January 2004 to July 2015.Results A total of 1 078 HIV/acquired immune deficiency syndrome(AIDS)children were treated with antiviral therapy.Before treatment,the average CD4+cell number was(466.8 ± 397.2)cells/μL. The percentages of children with CD4+cell count >750 cells/μL after 1-year,3-year,5-year and 8-year treatment were 54.31%,62.87%,68.46% and 74.19%,respectively.Virological failure occurred in 150 HIV/AIDS children(13.9%),and the virological failure rate was 4.3/100 child-years.Among those 150 patients with virological failure,104 cases(69.33%)exhibited genetic resistance to antiretroviral drugs.The prevalent mutations associated with drug resistance were M 184V/I(75.0% [78/104]), K103N(43.3%[45/104]),G190A(29.8%[31/104]),Y181C(22.1%[23/104]),T215Y/F(20.2%[21/104]).Conclusions After long-term antiretroviral treatment,most of the HIV-infected children have restored the immunity and suppressed HIV viral replication successfully.HIV resistance is the main cause of virological failure.Drug resistance mutations mainly occur in nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor,and the resistance rate of proteinase inhibitor is low.Early genetic resistance testing and switch to second-line therapy will improve the treatment outcome.