OBJECTIVE: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. DESIGN: 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 toTPV/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.
RCT Entities:
OBJECTIVE: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatricpatients. DESIGN: Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. METHODS:HIV-1-infectedpatients (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: Pieter L A Fraaij; Gwenda Verweel; Annemarie M C van Rossum; Ellen G van Lochem; Martin Schutten; Corry M R Weemaes; Nico G Hartwig; David M Burger; Ronald de Groot Journal: Clin Infect Dis Date: 2005-01-25 Impact factor: 9.079
Authors: Annemarie M C van Rossum; Sibyl P M Geelen; Nico G Hartwig; Tom F W Wolfs; Corry M R Weemaes; Henriëtte J Scherpbier; Ellen G van Lochem; Wim C J Hop; Martin Schutten; Albert D M E Osterhaus; David M Burger; Ronald de Groot Journal: Clin Infect Dis Date: 2002-03-04 Impact factor: 9.079
Authors: A Mocroft; B Ledergerber; J P Viard; S Staszewski; M Murphy; A Chiesi; A Horban; A-B E Hansen; A N Phillips; J D Lundgren Journal: J Infect Dis Date: 2004-10-28 Impact factor: 5.226
Authors: Jennifer R King; Sharon Nachman; Ram Yogev; Janice Hodge; Grace Aldrovandi; Michael D Hughes; Jie Chen; Andrew Wiznia; Bharat Damle; Edward P Acosta Journal: Pediatr Infect Dis J Date: 2005-10 Impact factor: 2.129
Authors: D M Gibb; T Duong; P A Tookey; M Sharland; G Tudor-Williams; V Novelli; K Butler; A Riordan; L Farrelly; J Masters; C S Peckham; D T Dunn Journal: BMJ Date: 2003-11-01
Authors: Katherine Luzuriaga; Margaret McManus; Lynne Mofenson; Paula Britto; Bobbie Graham; John L Sullivan Journal: N Engl J Med Date: 2004-06-10 Impact factor: 91.245
Authors: Gwenda Verweel; Mike Sharland; Hermione Lyall; Vas Novelli; Diane M Gibb; Gillian Dumont; Colin Ball; Ed Wilkins; Sam Walters; Gareth Tudor-Williams Journal: AIDS Date: 2003-07-25 Impact factor: 4.177
Authors: F van Leth; P Phanuphak; K Ruxrungtham; E Baraldi; S Miller; B Gazzard; P Cahn; U G Lalloo; I P van der Westhuizen; D R Malan; M A Johnson; B R Santos; F Mulcahy; R Wood; G C Levi; G Reboredo; K Squires; I Cassetti; D Petit; F Raffi; C Katlama; R L Murphy; A Horban; J P Dam; E Hassink; R van Leeuwen; P Robinson; F W Wit; J M A Lange Journal: Lancet Date: 2004-04-17 Impact factor: 79.321
Authors: Richard M Rutstein; Pearl Samson; Terry Fenton; Courtney V Fletcher; Jennifer J Kiser; Lynne M Mofenson; Elizabeth Smith; Bobbie Graham; Marina Mathew; Grace Aldrovani Journal: Pediatr Infect Dis J Date: 2015-02 Impact factor: 2.129
Authors: Joshua D Courter; Colleen J Teevan; Michael H Li; Jennifer E Girotto; Juan C Salazar Journal: Ther Clin Risk Manag Date: 2010-10-05 Impact factor: 2.423
Authors: Sharon Nachman; Nan Zheng; Edward P Acosta; Hedy Teppler; Brenda Homony; Bobbie Graham; Terence Fenton; Xia Xu; Larissa Wenning; Stephen A Spector; Lisa M Frenkel; Carmelita Alvero; Carol Worrell; Edward Handelsman; Andrew Wiznia Journal: Clin Infect Dis Date: 2013-10-21 Impact factor: 9.079