Mutations related to Antiretroviral Resistance identified by ultra-deep sequencing in HIV-1 infected children under Structured Interruptions of HAART

Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strate...

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Detalles Bibliográficos
Autores: Vázquez Guillén, José Manuel, Palacios Saucedo, Gerardo C., Rivera Morales, Lydia G., García Campos, Jorge, Ortiz López, Rocío, Noguera-Julian, Marc|||0000-0002-6194-1395, Paredes, Roger|||0000-0002-6553-691X, Vielma Ramírez, Herlinda J., Ramírez, Teresa, Chávez García, Marcelino, López Guillén, Paulo, Briones Lara, Evangelina, Sánchez Sánchez, Luz M., Vázquez Martínez, Carlos A., Rodríguez Padilla, Cristina
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:174694
Acceso en línea:https://ddd.uab.cat/record/174694
https://dx.doi.org/urn:doi:10.1371/journal.pone.0147591
Access Level:acceso abierto
Palabra clave:SIDA
VIH (Virus)
Antiretroviral resistance
Structured interruptions of HAART
Structured Treatment Interruptions (STI)
Descripción
Sumario:Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI.