title: Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil.
abstract: Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by polymerase chain reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients. In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel mutations that display subtype-specific predominance or occurrence.
authors.affiliation: 1 Departamento de Medicina, Universidade Federal do Rio Grande , Rio Grande, Brazil .
authors.forename: Maria F M
authors.initials: MFM
authors.lastname: Barral
authors.affiliation: 2 Departamento de Genética, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Arielly K P
authors.initials: AKP
authors.lastname: Sousa
authors.affiliation: 2 Departamento de Genética, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: André F
authors.initials: AF
authors.lastname: Santos
authors.affiliation: 2 Departamento de Genética, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Celina M
authors.initials: CM
authors.lastname: Abreu
authors.affiliation: 2 Departamento de Genética, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.affiliation: 2 Departamento de Genética, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil .|3 Programa de Genética, Instituto Nacional de Câncer , Rio de Janeiro, Brazil .
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D001938:Brazil; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV; antiretroviral therapy; epidemiology; reverse transcription