Browsing by Author "Fortuny, Claudia"

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    Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents
    (2008-09-12) Salazar, Juan C; Cahn, Pedro; Yogev, Ram; Negra, Marinella Della; Castelli-Gattinara, Guido; Fortuny, Claudia; Flynn, Patrica M; Giaquinto, Carlo; Ruan, Ping K; Smith, M Elizabeth; Mikl, Jaromir; Jelaska, Ante; for the PACTG 1051/BI Study Team
    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/m2 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.
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    Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
    (2009-09-24) Blanche, Stéphane; Bologna, Rosa; Cahn, Pablo; Rugina, Sorin; Flynn, Patricia; Fortuny, Claudia; Vis, Peter; Sekar, Vanitha; van Baelen, Ben; Dierynck, Inge; Spinosa-Guzman, Sabrina
    Objective: To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6–17 years). Design: Forty-eight-week, open-label, two-part, phase II study. Methods: In part I, 44 patients were randomized (1: 1 ratio) to receive a body weight-adjusted, adult-equivalent dose (group A) or a 20–33% higher DRV/r twice daily (b.i.d.) dose (group B). Pharmacokinetics, safety and efficacy were assessed following 2-week dosing (part I), which determined dosing for part II (evaluated 48-week safety and efficacy). Results: In part I, both groups met the protocol-specified criteria for pharmacokinetics and showed favorable tolerability and efficacy. The following body-weight doses were selected: DRV/r 375/50 mg b.i.d. (20–<30 kg), 450/60 mg b.i.d. (30–<40 kg) and 600/100 mg b.i.d. (≥40 kg); these gave an AUC24h, C0h and Cmax of 102, 114 and 112%, respectively, versus the corresponding mean adult pharmacokinetic parameter. In part II, 80 patients received DRV/r (median age: 14 years, mean baseline HIV-1 RNA: 4.64 log10copies/ml). One patient (1%) discontinued (treatment-unrelated grade 3 anxiety). An abnormal mean baseline triglyceride level was normalized at 48 weeks (P < 0.01). At week 48, 65% had at least 1.0 log10HIV-1 RNA reduction; 59 and 48% achieved HIV-1 RNA less than 400 and less than 50 copies/ml, respectively (time-to-loss-of-virologic response). Mean age-adjusted weight z-score increased by 0.2 (P = 0.003). Conclusion: In treatment-experienced children and adolescents, DRV/r showed comparable exposure to adults with appropriate dose selection, favorable safety and tolerability, improved body weight and significant virologic response. DRV/r is a valuable therapeutic option for this population. Introduction