Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure

• DOI: 10.1093/jac/dkab080
• Publication Date: 2021-03-02T20:10:33Z
• Authors: Santiago Jiménez ...; Carolina Beltrán-...; Miguel Gutiérrez-...; María Del Mar Santos; Luis Prieto; Talía Sainz; Sara Guillen; David Aguilera-Al...; Cristina Díez; Jose Ignacio Bern...; María José Mellado; José Tomás Ramos; África Holguín; Marisa Navarro; ; María José Mellado; Luis Escosa; Milagros García H...; Talía Sainz; Pablo Rojo; Luis Prieto-Tato; Cristina Epalza; José Tomás Ramos; Marta Illán; Sara Guillén; María Luisa Navarro; Jesús Saavedra; Mar Santos; Begoña Santiago; Santiago Jimenez ...; Itzíar Carrasco; Arantxa Berzosa; David Aguilera; Maria Angeles Muñ...; Miguel Ángel Roa; María Penín; Jorge Martínez; Katie Badillo; Ana Belén Jiménez; Adriana Navas; Eider Oñate; Itziar Pocheville; Elisa Garrote; Elena Colino; Jorge Gómez Sirvent; Mónica Garzón; Vicente Román; Raquel Angulo; Olaf Neth; Lola Falcón; Pedro Terol; Juan Luis Santos; Álvaro Vázquez; David Moreno; Francisco Lendínez; Estrella Peromingo; Beatriz Ruiz; Ana Grande; Francisco José Ro...; Carlos Pérez; Miguel Lillo; Begoña Losada; Mercedes Herranz; Matilde Bustillo; Miguel Lafuente; Pilar Collado; José Antonio Couc...; Leticia Vila; Consuelo Calviño; Ana Isabel Piqueras; Manuel Oltra; César Gavilán; Elena Montesinos; Marta Dapena; Cristina Álvarez; Beatriz Jiménez; Ana Gloria Andrés; Víctor Marugán; Carlos Ochoa; Ana Isabel Menasa...; Eloísa Cervantes; Pere Soler-Palacín; Maria Antoinette ...; Antonio Mur; Nuria Lopez; María Mendez; Lluıs Mayol; Teresa Vallmanya; Olga Calavia; Lourdes García; María Teresa Coll; Valentí Pineda; Neus Rius; Joaquín Dueñas; Clàudia Fortuny; Antoni Noguera-Ju...; María Luisa Montes; Eulalia Valencia; Rafael Rubio; Federico Pulido; Otilia Bisbal; Gabriel Gaspar Al...; Juan Berenguer; Cristina Díez; Teresa Aldamiz; Pedro Montilla; Elena Bermúdez; Maricela Valerio; José Sanz; Sari Arponen; Alejandra Gimeno; Miguel Cervero; Rafael Torres; Santiago Moreno; Ma Jesús Pérez; Santos del Campo; Pablo Ryan; Jesús Troya; Jesús Sanz; Juan Losa; Rafael Gómez; Miguel Górgolas; José Antonio Irib...; Francisco Rodríguez; Lydia Pascual; María José Aramburu; Ane Josune Goikoe...; Josefa Muñoz; Sofía Ibarra; Michele Hernández; Juan Luis Gómez S...; Jehovana Rodríguez; Miguel Ángel Cárd...; Luis Fernando Lóp...; Cristina Roca; Silvia Llaves; María José Ríos; Jesús Rodríguez; Virginia Palomo; Juan Pasquau; Coral García; José Hernández; Clara Martínez; Antonio Rivero; Ángela Camacho; Dolores Merino; Laura Corpa; Elisa Martínez; Fernando Mateos; José Javier Blanch; Miguel Torralba; Piedad Arazo; Gloria Samperiz; Celia Miralles; Antonio Ocampo; Guille Pousada; Álvaro Mena; Marta Montero; Miguel Salavert; Iván Castro; Sandra Cuéllar; María José Galindo; Ramón Ferrando; Joaquín Portilla; Irene Portilla; Félix Gutiérrez; Mar Masiá; Cati Robledano; Araceli Adsuar; Carmen Hinojosa; Jésica Abadía; Carlos Galera; Helena Albendín; Marian Fernández; José Ramón Blanco; Joaquín Burgos; Berta Torres; Elisa de Lazzari

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 <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.