Viral Suppression, Viral Failure, and Safety Outcomes in Children and Adolescents With HIV on Dolutegravir in Europe and Thailand

Background: Dolutegravir (DTG) is a preferred anchor antiretroviral therapy (ART) for children and adolescents with HIV (CAWH). Methods: We assessed the effectiveness and safety of DTG in CAWH aged 0-18 years at DTG start in routine care in Europe and Thailand, evaluating viral suppression (viral load [VL] <50 copies/mL), cumulative incidence and associated factors of viral failure (VF; confirmed VL ≥400 copies/mL) and safety outcomes. Results: Of 1230 CAWH on DTG, 49% were female. At DTG start, median (IQR) age was 14 (11-16) years, 10% were ART-naive, 49% ART-experienced/suppressed (VL <200 copies/mL), 13% ART-experienced/viremic (VL ≥200 copies/mL), and 28% ART-experienced/unknown VL. Median duration on DTG was 93 (49-163) weeks. Virall suppression was 88%-91% throughout follow-up. Cumulative incidence (95% CI) of VF at weeks 96 and 144 was 4.3% (3.1%-6.1%) and 8.3% (6.2%-11.1%). Increased risk of VF was associated with female sex, ART-experienced/viremic, advanced/severe immunosuppression, previous treatment failure, and region (P < .05, adjusting for age, sex and ART/VL status). The risk of VF was lower on DTG than CAWH on protease-inhibitor-based regimens (P < .001). Among 1146 with clinical data, 26 (2%) experienced 52 DTG-related adverse events, including 5 serious adverse events. Of 849 with laboratory data, 44 (5%) had 54 grade ≥3 events (<1 per 100 person-years). DTG discontinuation by weeks 96 and 144 was 5.0% (3.8%-6.7%) and 9.5% (7.5%-12.0%). Conclusions: DTG was well tolerated, with ∼90% virally suppressed <50 copies/mL. VF was low overall but was significantly higher in children/adolescents ART-experienced and viraemic at DTG start, requiring close monitoring.