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48-week lipid- and glucose-related safety profile of darunavir/ritonavir in treatment-experienced, paediatric patients in DELPHI
Presented by Tammy Meyers (South Africa).
T. Meyers1, E. Joao2, J.H. Pilotto3, J. Pinto4, B. Van Baelen5, L. Lavreys5, S. Spinosa-Guzman5, S. Blanche6
1Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa, 2Hospital Dos Servidores Do Estado, Rio De Janeiro, Brazil, 3Hospital Geral De Nova Iguacu - HGNI DST/AIDS, Nova Iguacu, Brazil, 4Universidade Federal De Minas Gerais, Belo Horizonte, Brazil, 5Tibotec BVBA, Mechelen, Belgium, 6Hôpital Necker Enfants Malades, Paris, France
Background: In the final 48-week analysis of phase II, open-label DELPHI, darunavir with low-dose ritonavir (DRV/r) showed good virological response rates and favourable safety profile in treatment-experienced, HIV-1-infected paediatric patients. At Week 48, 48% achieved HIV-1 RNA < 50 copies/mL (time-to-loss of virologic response).
Methods: Patients received twice-daily DRV/r (DRV 11-19mg/kg and RTV 1.5-2.5mg/kg bid) for 48 weeks: 20-< 30kg, 375/50mg bid (n=20); 30-< 40kg, 450/60mg bid (n=24); ≥40kg, 600/100mg bid (n=36), plus optimised background regimen (≥2 NRTIs/NNRTIs/enfuvirtide). Lipid-lowering agents were disallowed. Patients fasted for ≥10 hours before blood sampling at baseline and Week 48. Lipid and glucose-related safety findings are reported.
Results: 80 patients (71% male; median 14y [range: 6-17]) received DRV/r. Mean baseline HIV-1 RNA: 4.64 log10 copies/mL, median baseline absolute CD4: 330 cells/mm3. All patients previously used ≥2 NRTIs, 79% NNRTIs, 96% PIs and 10% enfuvirtide. One patient (1%) discontinued due to grade 3 anxiety unrelated to treatment. Three patients (4%) had grade 2-4 treatment-related lipid abnormalities reported as AEs (two grade 2 LDL elevation; one grade 3 hypercholesterolemia); none led to permanent discontinuation. No grade 4 lipid-related AEs or any glucose-related AEs were reported. Clinically and statistically significant changes in lipid levels were observed (Figure).
[DELPHI: Mean lipid & glucose levels at BL & W48]
Conclusions: DRV/r was effective and generally well-tolerated in this treatment-experienced, paediatric population at Week 48. A clinically relevant reduction in triglycerides from baseline to 48 weeks was seen, possibly reflecting the switch from previous regimens prior to study start. No significant changes in glucose metabolism were observed.
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