title: Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy.
abstract: OBJECTIVE
  To investigate the longitudinal pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r) in HIV-infected infants initiating combination antiretroviral therapy (cART) between 2 weeks and 6 months of age.
  
  
  METHODS
  A prospective, open-label, multicenter Phase I/II study of LPV/r-based cART at a dose of 300/75 mg/m(2)/dose LPV/r twice daily. Intensive pharmacokinetic sampling at 12 months of age and quarterly predose LPV concentrations were collected and safety, virologic and immunologic responses were monitored every 4-12 weeks up to 252 weeks.
  
  
  RESULTS
  Thirty-one HIV-infected infants enrolled into two age cohorts, 14 days to <6 weeks and 6 weeks to <6 months; 29 completed ≥48 weeks of follow-up (median = 123 weeks, range 4-252). At 12 months of age, median LPV area under the curve was comparable for both age cohorts and similar to older children and adults. At week 48, 22 of 31 patients (71%) had HIV-1 RNA <400 copies/ml and 11 of 15 (73%) had <50 copies/ml; 29 of 31 achieved HIV-1 RNA <400 copies/ml on study treatment and 19 (66%) remained durably suppressed until the end of study; viral suppression correlated with a higher percentage of predose time points exceeding the LPV target of 1 μg/ml (92 vs. 71%, P = 0.002).
  
  
  CONCLUSIONS
  LPV/r at 300/75 mg/m(2)/dose as part of a cART regimen resulted in viral suppression through 96 weeks of treatment in >65% of young infants. Due to initially low LPV exposure in infants <6 weeks of age, frequent dose adjustment for weight gain is advisable and consideration should be given to studying a higher dose for very young infants.
authors.affiliation: Division of Infectious Diseases, Children's Memorial Hospital, Northwestern University's Feinberg School of Medicine, Chicago, Illinois, USA. echadwick@northwestern.edu
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Chadwick
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Carmelita G
authors.initials: CG
authors.lastname: Alvero
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Pinto
authors.forename: Brian L
authors.initials: BL
authors.lastname: Robbins
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Heckman
authors.forename: Paul E
authors.initials: PE
authors.lastname: Palumbo
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
mesh_terms: D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir