title: Lopinavir/ritonavir-based antiretroviral therapy in human immunodeficiency virus type 1-infected naive children: rare protease inhibitor resistance mutations but high lamivudine/emtricitabine resistance at the time of virologic failure.
abstract: BACKGROUND
  Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line antiretroviral therapy for children <6 years of age.
  
  
  METHODS
  We included all the human immunodeficiency virus (HIV) type 1-infected highly active antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between 2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an HIV-RNA ≥50 copies/mL. Resistance genotypic test was performed in case of VF.
  
  
  RESULTS
  A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV RNA and percentage of CD4 cell count was 5.5 log₁₀ copies/mL (4.6-6) and 15% (8-27.5), respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months (18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The risk factors of primary VF were a young age and a low socioeconomic status. The genotypic resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18 children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant virus. No virus resistant to zidovudine or abacavir was found.
  
  
  CONCLUSIONS
  In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPV-resistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk factors of poor adherence.
authors.affiliation: Unité d'Immunologie, Hématologie et Rhumatologie pédiatriques, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France. pierre.frange@nck.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Nelly
authors.initials: N
authors.lastname: Briand
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-fenoel
authors.forename: Florence
authors.initials: F
authors.lastname: Veber
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000494:pharmacology*; D061466:Lopinavir; D008297:Male; D009154:Mutation; D010297:Paris; D011744:Pyrimidinones / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D003841:Deoxycytidine; D061466:Lopinavir; D019259:Lamivudine; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D000068679:Emtricitabine; D019438:Ritonavir