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. Design Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses plus optimized background regimen (OBR). Methods HIV-1-infected patients (2–18 years) with plasma viral load (VL) ≥1500 copies/mL were randomized to TPV/r 290/115 mg/m2 or TPV/r 375/150 mg/m2 BID oral solution plus OBR. Week 48 efficacy, safety and tolerability results were evaluated. Results Children (n=115; 97% treatment experienced) were randomized to low or high dose. 88 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 VL <400 copies/mL and 34.5% and 35.1%, respectively, achieved VL <50 copies/mL. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase (ALT) elevations were observed in 6.3% of patients. No Grade 4 ALT or Grade 3/4 aspartate aminotransferase elevations were reported. Conclusions TPV/r achieved a sustained virologic response, showed a good safety profile and was tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.

Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents

“…It is also worth noting that tenofovir was made available to this population and that lamivudine was the most commonly used NRTI. The virologic results in this study compare favorably to those recently obtained with other new protease inhibitors in treatment-experienced children and adolescents [16][17][18][19].…”

Long-term Safety and Efficacy of Atazanavir-based Therapy in HIV-infected Infants, Children and Adolescents

“…18 Among 115 ARV-experienced patients 2–18 years receiving one of two doses of tipranavir/RTV based CART, 39.7–45.6% had VL< 400cpm at 48 weeks. 22 …”

Safety and Efficacy of Darunavir/Ritonavir in Treatment-experienced Pediatric Patients

“…[26][27][28][29] For example, in 100 treatment-naïve children aged 6 months to 12 years, lopinavir/ritonavir, 79% of patients had HIV RNA levels <400 copies/mL at week 48 (ITT: missing = failure). 26 Also, in Pediatric AIDS Clinical Trials Group 1020 in 41 children and adolescents aged from 3 to <18 years, atazanavir/ritonavir based treatment showed a 81% (13 of 16) response (<50 copies/mL) rate in antiretroviral-naïve patients and 24% (6 of 25) in antiretroviralexperienced patients at 48 weeks.…”