title: Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents.
abstract: OBJECTIVE
  To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients.
  
  
  METHODS
  Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen.
  
  
  METHODS
  HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated.
  
  
  RESULTS
  Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported.
  
  
  CONCLUSIONS
  TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.
authors.affiliation: Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, Connecticut 06106, USA. jsalaza@ccmckids.org
authors.forename: Juan C
authors.initials: JC
authors.lastname: Salazar
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Marinella Della
authors.initials: MD
authors.lastname: Negra
authors.forename: Guido
authors.initials: G
authors.lastname: Castelli-Gattinara
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Patrica M
authors.initials: PM
authors.lastname: Flynn
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Ping K
authors.initials: PK
authors.lastname: Ruan
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Smith
authors.forename: Jaromir
authors.initials: J
authors.lastname: Mikl
authors.forename: Ante
authors.initials: A
authors.lastname: Jelaska