48-week data for darunavir/ritonavir (DRV/r) in treatment-experienced children and adolescents

48-week data was presented from the DELPHI (TMC114-C212) study. DELPHI is a multi site open-label, two-part Phase II study assessing the safety and efficacy of DRV/r plus OBR in treatment-experienced children and adolescents.

Children were dosed according to body weight for >/=48 weeks: 20-<30kg, 375/50mg bid (20 patients); 30-<40kg, 450/60mg bid (24 patients); >/=40kg, 600/100mg bid (36 patients). PK, safety and efficacy (viral load, CD4 % and CD4 counts) were evaluated throughout the study.

80 children with a median age of 14 years (range: 6-17 years) of which 71% were male received DRV/r. At baseline their mean viral load was 4.64 log, median CD4 was 330 cells/mm3 and CD4 % was 17%. They had a median of 3 primary PI mutations, 11 PI RAMs (65% had >/=10 PI RAMs), 2 NNRTI and 4 NRTI RAMs.

The investigators reported that target DRV PK concentrations for treatment-experienced adults were achieved across all ages and weight bands, which confirmed the dose selection.

The majority of patients (74, 93%) experienced one AE. The most frequently reported were: fever, cough, upper respiratory tract infection and diarrhea. Most were grade 1/2. 21 (26%) patients had grade 3/4 AEs but most were considered to be unrelated to DRV/r. 11 (14%) of patients (14%) experienced serious AEs but there were no deaths. One patient discontinued the study because of grade 3 anxiety but this was not considered to be DRV/r related. 6 pts (8%) had grade 2-4 AEs possibly related to DRV/r.

At week 48, 65% of patients had =1.0 log10 viral load reduction (TLOVR); 59% and 48% were undetectable to <400 and <50 copies/mL (TLOVR), respectively. Their mean CD4 increase was 147 cells/mm3.

The investigators noted that predictive analyses will be performed to evaluate the contribution of the OBR to response rates in this population.

Blanche S, Bologna R, Cahn P et al. 48-wk safety and efficacy of Darunavir/ritonavir (DRV/r) in treatment-experienced children and adolescents in DELPHI. 48th ICAAC, 25-28 October 2008. Washington. Abstract H-894.