title: Impact of lopinavir-ritonavir exposure in HIV-1 infected children and adolescents in Madrid, Spain during 2000-2014.
abstract: BACKGROUND
  The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain.
  
  
  METHODS
  Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure. Drug resistance mutations (DRM) were identified in viruses from samples collected until 2011. We predicted drug susceptibility to 19 antiretrovirals among those carrying DRM using the Stanford's HIVdb Algorithm.
  
  
  RESULTS
  A total of 199 (37.3%) of the 534 patients from the cohort were exposed to LPV/r during 2000-2014 in first (group 1), second (group 2) or more line-therapies (group 3). Patients were mainly Spaniards (81.9%), perinatally infected (96.5%) with subtype-B (65.3%) and HIV-diagnosed before year 2000 (67.8%). The mean age at first LPV/r exposure was 9.7 years. After protease-inhibitor exposure, viral suppression was higher in groups 1 and 2 than in group 3. Viral suppression occurred in 87.5%, 68.6% and 64.8% patients from groups 1, 2 and 3, respectively. Among the 64 patients with available resistance data during LPV/r treatment, 27(42.3%) carried DRM to protease-inhibitor, 28 (58.3%) to reverse-transcriptase-inhibitors and 21 (43.7%) to non-reverse-transcriptase-inhibitors. Darunavir/ritonavir, atazanavir-ritonavir and tipranavir/ritonavir presented the highest susceptibility and nelfinavir the lowest.
  
  
  CONCLUSIONS
  A better lymphocyte recovering occurred when protease-inhibitor was taken as part of a first-line regimen and a higher number of patients reached viral suppression. The least compromised antiretrovirals for rescue antiretroviral regimens, according to DRM in the LPV/r-exposed-paediatric cohort, were mainly the new protease inhibitors.
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital RamÓn y Cajal-IRYCIS and CIBER-ESP, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rojas Sánchez
authors.affiliation: Infectious Diseases Department, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Prieto
authors.affiliation: Molecular Inmuno-Biology Laboratory, Hospital Universitario Gregorio Marañón-IISGM and CIBER-BBN, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Jiménez De Ory
authors.affiliation: Infectious Diseases Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fernández Cooke
authors.affiliation: Infectious Diseases Unit, Paediatric Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Navarro
authors.affiliation: Infectious Diseases Department, Hospital Clínico Universitario and Universidad Complutense, Madrid, Spain.
authors.forename: José Tomas
authors.initials: JT
authors.lastname: Ramos
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital RamÓn y Cajal-IRYCIS and CIBER-ESP, Madrid, Spain.
authors.forename: África
authors.initials: Á
authors.lastname: Holguín
mesh_terms: D000293:Adolescent; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D019438:Ritonavir / Q000627:therapeutic use*; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000821:virology
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir