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 (bid) 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 bid (20–< 30 kg), 450/60 mg bid (30–< 40 kg) and 600/100 mg bid (≥ 40 kg); these gave an AUC 24h, C 0h and C max 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 log 10 copies/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 log 10 HIV-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.