title: Predictive factors of virologic success in HIV-1-infected children treated with lopinavir/ritonavir.
abstract: Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level.
authors.affiliation: Service de Virologie-EA 3620, Hôpital Necker Enfants Malades, Paris, France. constance.delaugerre@nck.ap-hop-paris.fr
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Teglas
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Paula
authors.initials: P
authors.lastname: Vaz
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Florence
authors.initials: F
authors.lastname: Veber
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
mesh_terms: D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D011446:Prospective Studies; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir