title: Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain.
abstract: BACKGROUND
  Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were identified in HIV-infected children from Madrid, Spain.
  
  
  METHODS
  Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).
  
  
  RESULTS
  In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.
  
  
  CONCLUSIONS
  HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, FiBIO-IRYCIS, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: de Mulder
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Yebra
authors.forename: Leticia
authors.initials: L
authors.lastname: Martín
authors.forename: Luís
authors.initials: L
authors.lastname: Prieto
authors.forename: María José
authors.initials: MJ
authors.lastname: Mellado
authors.forename: Pablo
authors.initials: P
authors.lastname: Rojo
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Santiago
authors.initials: S
authors.lastname: Jiménez de Ory
authors.forename: José Tomas
authors.initials: JT
authors.lastname: Ramos
authors.forename: Africa
authors.initials: A
authors.lastname: Holguín
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013030:Spain; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054302:pol Gene Products, Human Immunodeficiency Virus