title: Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals.
abstract: BACKGROUND
  Many human immunodeficiency virus type 1 (HIV-1)-infected children have already failed treatment with 2 or even 3 classes of antiretrovirals. Coformulation of lopinavir with low dose ritonavir exhibits a potent antiretroviral effect. However, the data in heavily pretreated children are still scarce. This study evaluated the safety and effectiveness of combination therapy including lopinavir/ritonavir in children with prior exposure to all classes of oral antiretrovirals.
  
  
  METHODS
  This was an open label multicenter observational study, in which data were reviewed according to a standardized protocol. The study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced with the 3 classes of oral antiretrovirals, in whom a lopinavir/ritonavir-containing regimen was started.
  
  
  RESULTS
  By March 2003, 45 patients had been treated with lopinavir/ritonavir for a median of 18 months (range, 3-28). The median age at baseline was 9.7 years (range, 4.3-17.1). The median times of prior treatment were 88 months (range, 31-145) with nucleoside reverse transcription inhibitors and 42 months (range, 19-63) with protease inhibitors. Twenty-five patients were classified as Centers for Disease Control and Prevention clinical category C. Median values for absolute and percentage CD4 at baseline were 501 (range, 6-1512) and 19% (range, 0.5-49), respectively, and plasma HIV-RNA was 5.0 log10 copies/mL (range, 4.1-6.1). During follow-up, 11 (24%) children switched from liquid to solid formulation. At 48 weeks, the median values for absolute and percentage CD4 increased by 199 cells/microL and 3%, respectively, and median plasma viral load declined 1.75 log10 copies/mL. Forty-two percent of children achieved a plasma RNA of <400 copies/mL (intent to treat analysis). Baseline genotypic resistance was available in 40 children. Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06). Adverse events were described in 18 children. Three children permanently discontinued and 4 transiently withdrew lopinavir/ritonavir. At 12 months, there were mild but not significant increases in plasma cholesterol and triglycerides.
  
  
  CONCLUSIONS
  Lopinavir/ritonavir when given as part of salvage regimen is well-tolerated, although switching to pills is frequently required. The regimen has a potent and durable antiretroviral activity in most heavily pretreated children, despite the presence of multiple mutations to all classes of oral antiretrovirals.
authors.affiliation: Hospital 12 Octubre, Madrid, Spain. jramos.hdoc@salud.madrid.org
authors.forename: José T
authors.initials: JT
authors.lastname: Ramos
authors.forename: María Isabel
authors.initials: MI
authors.lastname: De José
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dueñas
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Raúl
authors.initials: R
authors.lastname: González-Montero
authors.forename: María José
authors.initials: MJ
authors.lastname: Mellado
authors.forename: Antonio
authors.initials: A
authors.lastname: Mur
authors.forename: Marisa
authors.initials: M
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Otero
authors.forename: Itziar
authors.initials: I
authors.lastname: Pocheville
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.forename: Esther
authors.initials: E
authors.lastname: Cabrero
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000009:adverse effects* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019438:Ritonavir