Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
Authors: Jiménez de Ory Santiago , Beltrán-Pavez Carolina , Gutiérrez-López Miguel , Santos María Del Mar , Prieto Luis , Sainz Talía , Guillen Sara , Aguilera-Alonso David , Díez Cristina , Bernardino Jose Ignacio , Mellado María José , Ramos José Tomás , Holguín África , Navarro Marisa ,   the Paediatric Cohort of the Spanish National AIDS Network (CoRISpe and CoRISpe-FARO), Mellado María José , Escosa Luis , Hortelano Milagros García , Sainz Talía , Rojo Pablo , Prieto-Tato Luis , Epalza Cristina , Ramos José Tomás , Illán Marta , Guillén Sara , Navarro María Luisa , Saavedra Jesús , Santos Mar , Santiago Begoña , de Ory Santiago Jimenez , Carrasco Itzíar , Berzosa Arantxa , Aguilera David , Muñoz-Fernández Maria Angeles , Roa Miguel Ángel , Penín María , Martínez Jorge , Badillo Katie , Jiménez Ana Belén , Navas Adriana , Oñate Eider , Pocheville Itziar , Garrote Elisa , Colino Elena , Sirvent Jorge Gómez , Garzón Mónica , Román Vicente , Angulo Raquel , Neth Olaf , Falcón Lola , Terol Pedro , Santos Juan Luis , Vázquez Álvaro , Moreno David , Lendínez Francisco , Peromingo Estrella , Ruiz Beatriz , Grande Ana , Romero Francisco José , Pérez Carlos , Lillo Miguel , Losada Begoña , Herranz Mercedes , Bustillo Matilde , Lafuente Miguel , 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 , Soler-Palacín Pere , Frick Maria Antoinette , Mur Antonio , Lopez Nuria , Mendez María , Mayol Lluıs , Vallmanya Teresa , Calavia Olga , García Lourdes , Coll María Teresa , Pineda Valentí , Rius Neus , Dueñas Joaquín , Fortuny Clàudia , Bernardino Antoni Noguera-Julian Ignacio , Montes María Luisa , Valencia Eulalia , Rubio Rafael , Pulido Federico , Bisbal Otilia , Alonso Gabriel Gaspar , Berenguer Juan , Díez Cristina , Aldamiz Teresa , Montilla Pedro , Bermúdez Elena , Valerio Maricela , Sanz José , Arponen Sari , Gimeno Alejandra , Cervero Miguel , Torres Rafael , Moreno Santiago , Pérez Ma Jesús , del Campo Santos , Ryan Pablo , Troya Jesús , Sanz Jesús , Losa Juan , Gómez Rafael , Górgolas Miguel , Iribarren José Antonio , Rodríguez Francisco , Pascual Lydia , Aramburu María José , Goikoetxea Ane Josune , Muñoz Josefa , Ibarra Sofía , Hernández Michele , Sirvent Juan Luis Gómez , Rodríguez Jehovana , Cárdenes Miguel Ángel , López-Cortés Luis Fernando , Roca Cristina , Llaves Silvia , Ríos María José , Rodríguez Jesús , Palomo Virginia , Pasquau Juan , García Coral , Hernández José , Martínez Clara , Rivero Antonio , Camacho Ángela , Merino Dolores , Corpa Laura , Martínez Elisa , Mateos Fernando , Blanch José Javier , Torralba Miguel , Arazo Piedad , Samperiz Gloria , Miralles Celia , Ocampo Antonio , Pousada Guille , Mena Álvaro , Montero Marta , Salavert Miguel , Castro Iván , Cuéllar Sandra , Galindo María José , Ferrando Ramón , Portilla Joaquín , Portilla Irene , Gutiérrez Félix , Masiá Mar , Robledano Cati , Adsuar Araceli , Hinojosa Carmen , Abadía Jésica , Galera Carlos , Albendín Helena , Fernández Marian , Blanco José Ramón , Burgos Joaquín , Torres Berta , de Lazzari Elisa 
Published: March 2021

Abstract

Objectives
We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples.

Methods
We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA &lt;50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool.

Results
Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6–23.1) with 4 years (IQR 2.1–6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART.

Conclusions
The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.