title: Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population.
abstract: BACKGROUND
  Although dual-boosted protease inhibitors regimen is not recommended in children with HIV infection, such a strategy could be useful in subjects with a complex resistance profile. This study was aimed at assessing the long term efficacy and safety of a double-boosted protease inhibitor combination, fosamprenavir (fAVP) and atazanavir/ritonavir (ATV/r) in a cohort of HIV-infected children and adolescents who had failed with nucleoside reverse transcriptase inhibitors.
  
  
  METHODS
  Seven vertically infected children and adolescents who had previously failed highly active antiretroviral therapy and were resistant to nucleoside reverse transcriptase inhibitors, received a dual protease inhibitor (PI) regimen including fAVP plus ATV/r for 42 months. The patients were assessed at baseline, every month for the first 24 weeks of therapy and every 3 months until month 32. Physical examination, CD4+ cell count, HIV-RNA viral load, lipid profile and hepatic function were assessed throughout the follow up.
  
  
  RESULTS
  During the study no serious adverse events were reported. CD4 absolute number increased over-time in all subjects. At baseline the median HIV-RNA was 6562 cp/mL (ranging 1048 -102772 cp/mL) and rapidly decreased below the limit of detection (50 cp/mL) after 2 months of the new treatment and remained undetectable in all cases through the entire study period. At the beginning of the study all cases showed a normal lipid profile. During the study period, 4/7 subjects showed total cholesterol, low density lipoprotein and triglyceride levels >97th cent.le for the males and 94th cent.le for the females. HDL cholesterol showed protective values. Hepatic enzymes remained stable during the entire observation, whereas total bilirubin showed toxicity II/III grade in 6/7 subjects. No change in fat redistribution and insulin resistance was observed.
  
  
  CONCLUSIONS
  Dual-boosted protease inhibitor therapy was virologically and immunologically effective and it could be considered as a possible alternative to a rescue regimen in children and adolescents. However, hypercholesterolemia and hypertriglyceridemia need close follow-up and may limit the use of this therapeutic option.
authors.affiliation: Department of Biomedical and Clinical Science Luigi Sacco, Infectious Diseases, University of Milan, Milan, Italy. stefano.rusconi@unimi.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.forename: Vania
authors.initials: V
authors.lastname: Giacomet
authors.forename: Chiara
authors.initials: C
authors.lastname: Mameli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viganò
authors.forename: Ottavia
authors.initials: O
authors.lastname: Viganò
authors.forename: Fulvio
authors.initials: F
authors.lastname: Adorni
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Gian Vincenzo
authors.initials: GV
authors.lastname: Zuccotti
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage*; D002648:Child; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D010755:Organophosphates / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D010755:Organophosphates; D011725:Pyridines; D012367:RNA, Viral; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; C426859:fosamprenavir