Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents

AIDS. 2008 Sep 12;22(14):1789-98. doi: 10.1097/QAD.0b013e32830c481b.

Abstract

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 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.

Trial registration: ClinicalTrials.gov NCT00076999.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / blood
  • Blood Coagulation Disorders / chemically induced
  • Child
  • Child, Preschool
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1*
  • Humans
  • Logistic Models
  • Male
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Pyrones / administration & dosage*
  • Pyrones / adverse effects
  • Pyrones / therapeutic use
  • Ritonavir / administration & dosage*
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use
  • Sulfonamides
  • Treatment Outcome
  • Viral Load
  • Vomiting / chemically induced

Substances

  • Anti-HIV Agents
  • Biomarkers
  • HIV Protease Inhibitors
  • Pyridines
  • Pyrones
  • Sulfonamides
  • Alanine Transaminase
  • Ritonavir
  • tipranavir

Associated data

  • ClinicalTrials.gov/NCT00076999