A NEW study has identified more effective and safe second-line antiretroviral therapy (ART) options for children with HIV following failure of first-line treatment.
In this open-label trial using a 2-by-4 factorial design, 919 children with HIV and prior first-line ART failure were randomised to receive either tenofovir alafenamide fumarate (TAF)-emtricitabine or standard nucleoside backbone therapy (abacavir or zidovudine plus lamivudine). Participants were further assigned to one of four anchor drugs: dolutegravir, ritonavir-boosted darunavir, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir. The primary endpoint was achieving a viral load of less than 400 copies per millilitre at 96 weeks. Researchers tested for noninferiority or superiority of TAF-emtricitabine and each anchor drug, and also assessed safety outcomes across regimens.
The median age of participants was 10 years, with over half being male, and median baseline viral load was 17,573 copies/mL. By Week 96, TAF-emtricitabine was found to be superior to standard backbone therapy, with 6.3 percentage points more children achieving viral suppression (95% CI: 2.0–10.6; P=0.004). Among anchor drugs, dolutegravir significantly outperformed ritonavir-boosted lopinavir and atazanavir combined, with a 9.7 percentage point difference in viral suppression (95% CI: 4.8–14.5; P<0.001). Ritonavir-boosted darunavir showed a modest benefit (5.6 percentage points; 95% CI: 0.3 –11.0), but did not meet the trial’s predefined significance threshold (P=0.04). Ritonavir-boosted atazanavir was noninferior to ritonavir-boosted lopinavir. One death was reported, and serious adverse events occurred in 3.2% of participants, with no meaningful differences between treatment groups.
These results provide strong evidence supporting the use of dolutegravir and TAF-emtricitabine as preferred components of second-line ART in children. Their favourable efficacy and safety profiles may help shape future paediatric HIV treatment guidelines.
Reference
Musiime V et al; CHAPAS-4 Trial Team. Second-line antiretroviral therapy for children living with HIV in Africa. N Engl J Med. 2025;392(19):1917-32.
