title: Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team.
abstract: BACKGROUND
  Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear.
  
  
  OBJECTIVE
  To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy.
  
  
  METHODS
  The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks.
  
  
  METHODS
  Pediatric HIV research clinics in the United States and Puerto Rico.
  
  
  METHODS
  Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years.
  
  
  METHODS
  Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97).
  
  
  METHODS
  Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups.
  
  
  RESULTS
  At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively (P<.001). Through study week 48, 70% of children continued receiving their ritonavir-containing regimen. At study week 48, 42% of children receiving ritonavir plus 2 nucleosides compared with 27% of those receiving ritonavir and a single nucleoside had undetectable HIV RNA levels (P = .04); however, similar proportions in each group continuing initial therapy had HIV RNA levels of less than 10000 copies/mL (58% vs 48%, respectively; P = .19).
  
  
  CONCLUSIONS
  In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48.
authors.affiliation: Department of Pediatrics, State University of New York at Stony Brook, 11794-8111, USA. snachman@mail.som.sunysb.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Nachman
authors.forename: K
authors.initials: K
authors.lastname: Stanley
authors.forename: R
authors.initials: R
authors.lastname: Yogev
authors.forename: S
authors.initials: S
authors.lastname: Pelton
authors.forename: A
authors.initials: A
authors.lastname: Wiznia
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Mofenson
authors.forename: S
authors.initials: S
authors.lastname: Fiscus
authors.forename: M
authors.initials: M
authors.lastname: Rathore
authors.forename: E
authors.initials: E
authors.lastname: Jimenez
authors.forename: W
authors.initials: W
authors.lastname: Borkowsky
authors.forename: J
authors.initials: J
authors.lastname: Pitt
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Wells
authors.forename: K
authors.initials: K
authors.lastname: McIntosh
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D019438:Ritonavir