This was an open-label, randomized trial involving children in Uganda, Zambia, and Zimbabwe experiencing first-line NNRTI-based treatment failure.  Participants were randomly assigned to one of two backbones (TAF/FTC or standard care with ABC/3TC or ZDV/3TC) and were simultaneously assigned to one of four anchors (dolutegravir or ritonavir-boosted darunavir, atazanavir, or lopinavir).  Median age was 10 years (IQR 8-13), 54.1% were male, median VL 17,573 copies/mL (IQR 5,549-55,700) and CD4 669 cells/mm³ (IQR 413-971).  44.1% and 55.9% of participants had been on NVP and EFV based therapy, respectively.  At 96 weeks, 406/454 (89.4%) of participants on TAF/FTC had VL < 400 copies/mL vs. 378/454 (83.3%) on SOC, meeting the non-inferiority margin; there were no significant differences in adverse events or events leading to ART modification.  Although there was a slightly greater reduction in creatinine clearance in the TAF/FTC group, phosphate excretion was similar and no participant discontinued TAF due to renal dysfunction.  At 96 weeks, 92.0% of participants on DTG, 88.3% on DRV/r, 84.3% on ATV/r, and 80.7% on LPV/r had VL < 400 copies/mL.  There were no significant differences in ART modification rates [by anchor drug] due to adverse events.  Mean cost per participant of TAF/FTC-based treatment was lower than SOC, and DTG was the least costly anchor.

These results suggest that second-line pediatric ART regimens using a TAF/FTC backbone achieve virologic suppression at higher rates compared to those using ABC/3TC or ZDV/3TC, and that both DTG and DRV/r achieved higher suppression rates compared to ATV/r and LPV/r.  Overall, there were no significant safety concerns associated with TAF use over 96 weeks, and no negative effects on bone health or cases of tubulopathy were observed.  Investigators call for further development of child-friendly formulations involving fixed-dose TAF/FTC for WHO prioritization and incorporation into future treatment guidelines especially for resource limited settings.