Integrase inhibitors in children and adolescents: clinical use and resistance
Authors: Torres-Fernandez David , Jiménez de Ory Santiago , Fortuny Claudia , Sainz Talía , Falcón Dolores , Bernal Enrique , Jiménez Miguel Cervero , Vilasaró Marta Navarro , Epalza Cristina , Navarro Marisa , Ramos José Tomás , Holguín África , Prieto Luis ,   CoRIS and CoRISpe Spanish National Cohorts, CoRISpe and CoRISpe-FARO Cohort Working Group, Mellado María José , Escosa Luis , Hortelano Milagros García , Sainz Talía , Grasa Carlos , Rodr Paula , Rodríguez Paula , Rojo Pablo , Prieto-Tato Luis , Epalza Cristina , Tagarro Alfredo , Domínguez Sara , Ballesteros Álvaro , Ramos José Tomás , Illán Marta , Guillén Sara , Soto Beatriz , Navarro María Luisa , Saavedra Jesús , Berzosa Arantxa , Santos Mar , Aguilera David , Santiago Begoña , de Ory Santiago Jimenez , Muñoz-Fernández MªAngeles , Bermejo Amanda , Penín María , Martínez Jorge , Badillo Katie , Jiménez Ana Belén , Navas Adriana , Oñate Eider , Pocheville Itziar , Garrote Elisa , Colino Elena , Afonso Olga , Sirvent Jorge Gómez , Garzón Mónica , Román Vicente , Angulo Raquel , Neth Olaf , Falcón Lola , Terol Pedro , Luis Juan , Vázquez Álvaro , Carazo Begoña , Medina Antonio , Lendínez Francisco , Ibáñez Mercedes , Peromingo Estrella , Sánchez María Isabel , Ruiz Beatriz , Grande Ana , Romero Francisco José , Pérez Carlos , Pareja Marta , Losada Begoña , Herranz Mercedes , Nogueira Javier , Bustillo Matilde , Miralbés Sheila , Collado Pilar , Couceiro José Antonio , Vila Leticia , Calviño Consuelo , Piqueras Ana Isabel , Oltra Manuel , Gavilán César , Montesinos Elena , Dapena Marta , Álvarez Cristina , Jiménez Beatriz , Andrés Ana Gloria , Marugán Víctor , Ochoa Carlos , Menasalvas Ana Isabel , Cervantes Eloísa , Álvarez Beatriz , Soler-Palacín Pere , Frick Maria Antoinette , Lopez Nuria , Carreras Clara , Mayol Lluis , Vallmanya Teresa , Calavia Olga , García Lourdes , Pineda Valentí , Rius Neus , Dueñas Joaquín , Fortuny Claudia , Noguera-Julian Antoni , Bernardino Ignacio , Luisa Montes María , Valencia Eulalia , Delgado Ana , Rubio Rafael , Pulido Federico , Bisbal Otilia , Alonso Alfonso Monereo , Berenguer Juan , Díez Cristina , Aldamiz Teresa , Montilla Pedro , Bermúdez Elena , Valerio Maricela , Sanz Jose , Gimeno Alejandra , Cervero Miguel , Torres Rafael , Moreno Santiago , Perez María Jesús , del Campo Santos , Ryan Pablo , Troya Jesus , Sanz Jesus , Losa Juan , Gomez Rafael , Gorgolas Miguel , Iribarren Jose Antonio , Aramburu Marıa Jose , Martinez Lourdes , Goikoetxea Ane Josune , Ibarra Sofia , de la Peña Mireia , Hernandez Michele , Sirvent Juan Luis Gomez , Pelazas Ricardo , del Mar Alonso María , Alemán María Remedios , López Ana María , García Dácil , Rodriguez Jehovana , Cardenes Miguel Angel , Lopez-Cortes Luis Fernando , Roca Cristina , Llaves Silvia , Rios Marıa Jose , Rodrıguez Jesus , Palomo Virginia , Pasquau Juan , Garcia Coral , Hernandez Jose , Martinez Clara , Rivero Antonio , Camacho Angela , Merino Dolores , Raffo Miguel , Corpa Laura , Martinez Elisa , Mateos Fernando , Blanch Jose Javier , Torralba Miguel , Arazo Piedad , Samperiz Gloria , Miralles Celia , Ocampo Antonio , Pousada Guille , Mena Alvaro , Montero Marta , Salavert Miguel , Segarra Inma , Galindo Marıa Jose , Pretel Natalia , Portilla Joaquín , Portilla Irene , Gutierrez Felix , Masia Mar , Robledano Cati , Adsuar Araceli , Hinojosa Carmen , Monteagudo Begoña , Abadía Jesica , Galera Carlos , Albendin Helena , Fernandez Marian , Blanco Jose Ramon , Burgos Joaquín , Torres Berta , de Lazzari Elisa 
Published: August 2022

Abstract

Background
Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART.

Methods
Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database.

Results
Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0–16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1–3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir.

Conclusions
INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.