WEPDB0101 - Poster Discussion Session
24-week efficacy, safety, tolerability, and pharmacokinetics (PK) of darunavir/ritonavir (DRV/r) once daily (qd) in treatment-naive adolescents aged 12 to < 18 years in DIONE
Presented by Patricia Flynn (United States).
P. Flynn1, S. Blanche2, C. Giaquinto3, S. Komar4, A. Noguera-Julian5, S. Welch6, E. Lathouwers7, T. Van de Casteele7, P. Vis7, M. Opsomer7
1St. Jude Children's Research Hospital, Infectious Diseases, Memphis, United States, 2Hôpital Necker-Enfants Malades, Paris, France, 3Ospedale di Padova, Padova, Italy, 4Centre 'Clinic for Treatment of HIV-infected Children', Kiev, Ukraine, 5Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain, 6Birmingham Heartlands Hospital, Birmingham, United Kingdom, 7Tibotec BVBA, Beerse, Belgium
Background: DIONE (TMC114-C230; NCT00915655) is a Phase II, 48-week, open-label trial of DRV/r 800/100mg qd co-administered with zidovudine (ZDV)/lamivudine (3TC) or abacavir (ABC)/3TC in treatment-naïve, HIV-1-infected adolescents.
Methods: Patients aged 12-< 18 years, weighing ≥40kg, with viral load (VL) >1,000 copies/mL were eligible. For PK analysis, intensive sampling over 24 hours was performed after 2 weeks and sparse sampling after 4 and 24 weeks of dosing. Safety, efficacy and resistance were also assessed.
Results: 12 patients (66.7% female; mean age 14.6 years) were enrolled. Mean baseline VL was 4.72 log10 copies/mL, median CD4 count and percentage were 282 cells/mm3 and 18.3%, respectively. Six patients each received ZDV/3TC and ABC/3TC. All patients were susceptible to DRV and background NRTIs at baseline. After 24 weeks, 11/12 (92%) patients achieved VL < 50 copies/mL (ITT-TLOVR); all achieved VL < 400 copies/mL. Mean CD4 count (NC=F) and percentage increased by 175 cells/mm3 and 8%, respectively. No development of resistance-associated mutations or loss of susceptibility to PIs or background NRTIs was observed in patients with post-baseline genotype/phenotype data. No patients discontinued therapy. Adverse events (AE) and PK parameters are reported [Table]. Most frequently reported AEs (≥3 patients) were anaemia, nausea and vomiting (all n=3).
Median exposure was comparable to median exposure in treatment-naïve adults receiving DRV/r 800/100mg qd in ARTEMIS. All patients had C0h above EC50 for wild-type HIV (55ng/mL).
Conclusions: DRV/r 800/100mg qd co-administered with 2 NRTIs was effective and well-tolerated for the treatment of HIV-1-infected, ARV-naïve adolescents, with comparable exposure to treatment-naïve adults.
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