Viral Suppression, Viral Failure, and Safety Outcomes in Children and Adolescents With HIV on Dolutegravir in Europe and Thailand
Karen Scott, John O’Rourke, Charlotte Jackson, Luminita Ene, Luisa Galli, Tessa Goetghebuer, Cassidy Henegar, Christoph Königs, Magdalena Marczyńska, Lars Navér, Antoni Noguera‐Julián, P Paioni, José Tomás Ramos, Birgitte Smith, Wipaporn Natalie Songtaweesin, Vana Spoulou, Nattakarn Tantawarak, Anna Turkova, Vani Vannappagari, Алла Волоха, Alasdair Bamford, Hannah Castro, Elizabeth Chappell, G Valle, Caroline Foster, Sara Guillén Martín, Luis Manuel Prieto Tato, Thanyawee Puthanakit, Halyna Sherstiuk, Irina Shkurka, Sandra Soeria‐Atmadja, Ali Judd, Siobhan Crichton, Intira Jeannie Collins, Elizabeth Chappell, Siobhan Crichton, Intira Jeannie Collins, Giorgia Dalla Valle, Charlotte Duff, Kate Edgar, Carlo Giaquinto, Charlotte Jackson, Ali Judd, Laura Mangiarini, John O’Rourke, Karen Scott, Claire Thorne, St Pierre Cohort, Tessa Goetghebuer, Marc Hainaut, Wivine Tremerie, Marc Delforge, Thomas Ulrik Hoffmann, Sannie Brit Nordly, Birgitte Smith, Christoph Königs, Vana Spoulou, Luisa Galli, Elena Chiappini, Catiuscia Lisi, Carlotta Montagnani, Elisabetta Venturini, Magdalena Marczyńska, Jolanta Popielska, Maria Pokorska-Śpiewak, Agnieszka Ołdakowska, Konrad Zawadka, Magdalena Pluta, Małgorzata Doroba, Luminita Ene, María José Mellado, Luis Escosa, Milagros García Hortelano, Talía Sainz, Carlos Grasa, Paula Rodríguez, Jose Tomás Ramos, Pablo Rojo, Luis Manuel Prieto Tato, Cristina Epalza, Alfredo Tagarro, Sara Domínguez, Álvaro Ballesteros, Marta Illán, Arantxa Berzosa, Sara Guillén, Beatriz Soto, María Luisa Navarro, Jesús Saavedra, Mar Santos, Elena Rincón, David Aguilera, Begoña Santiago, Beatriz Lázaro Martín, Andrea López Suárez, Amanda Bermejo, María Penín, Jorge Martínez, Katie Badillo, Ana Belén Jiménez
Abstract
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.