Objective: Immune activation is associated with morbidity/mortality in HIV-infection despite antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation/inflammation were measured over 96 weeks in HIV-infected Ugandan children in CHAPAS-3 (ISRCTN69078957) and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques including next-generation sequencing. Results: Of 249 children included, 120 were HIV-infected ART-naive and 22 ART-experienced (median (IQR) age 2.8(1.7-4.0) and 6.5(5.9-9.2) years; median baseline CD4% 20(14-24) and 35(31-39)). 107 were HIV-uninfected controls. Median (IQR) CD4% increase was 17(12-22) at week-96 in ART-naive children, and viral load was<100 copies/mL in 76%/91% ART-naive/experienced. Immune activation decreased with ART. Children could be divided by immune activation markers into clusters: cluster-1 (majority HIV-uninfected); cluster-2 (mixed HIV-uninfected/ART-naive/ART-experienced); and cluster-3 (majority ART-naive). Immune activation was low in cluster-1, decreased in cluster-3, and persisted in cluster-2. Blood microbial DNA levels were negative/very low across groups, with no difference between clusters except Enterobacteriaceae (higher in cluster-1,p<0.0001). Conclusion: Immune activation decreased with ART, with marker-clustering indicating different activation patterns by HIV/ART status. Levels of bacterial DNA in blood were low regardless of HIV/ART/immune activation status. Microbial translocation did not drive immune activation in this setting.< Réduire