title: Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.
abstract: 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.
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Vazquez-Guillen
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Gerardo C
authors.initials: GC
authors.lastname: Palacios-Saucedo
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: Lydia G
authors.initials: LG
authors.lastname: Rivera-Morales
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Garcia-Campos
authors.affiliation: Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina and Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: Rocio
authors.initials: R
authors.lastname: Ortiz-Lopez
authors.affiliation: Institut de Recerca de la SIDA, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, España and Cátedra de la SIDA, Universitat de Vic, Vic, España.
authors.forename: Marc
authors.initials: M
authors.lastname: Noguera-Julian
authors.affiliation: Institut de Recerca de la SIDA, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, España and Cátedra de la SIDA, Universitat de Vic, Vic, España.
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: Herlinda J
authors.initials: HJ
authors.lastname: Vielma-Ramirez
authors.affiliation: Laboratorio Estatal de Salud Pública del Estado de Nuevo León, Secretaría de Salud, Nuevo León, México.
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Ramirez
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Chavez-Garcia
authors.affiliation: Unidad de Infectología "Dr. Juan I. Menchaca", Hospital General Regional No. 45, Instituto Mexicano del Seguro Social, Jalisco, México.
authors.forename: Paulo
authors.initials: P
authors.lastname: Lopez-Guillen
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Briones-Lara
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Luz M
authors.initials: LM
authors.lastname: Sanchez-Sanchez
authors.affiliation: División de Investigación, Departamento de Pediatría e Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vazquez-Martinez
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez-Padilla
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents