Safety and efficacy of boosted darunavir in treatment-experienced children and adolescents at 24 weeks

In an oral late breaker Sabrina Spinosa-Guzman from Tibotec presented data for duranavir boosted with ritonavir (DRV/r) in a group of treatment experienced children and adolescents.

TMC114-C212 or DELPHI, (Darunavir EvaLuation in Pediatric HIV-1-Infected treatment-experienced patients) trial is an ongoing 48-week, open-label, two-part phase II dose finding, pharmacokinetics, safety, tolerability and efficacy study in a group of paediatric patients aged 6 to 17 years.

In part I, patients were randomised to 2 DRV/r dose groups. In part II all patients received the recommended dose per body weight. Dr Spinosa-Guzman presented safety and efficacy results of part II from a primary analysis at 24 weeks.

In this study patients received doses according to weight bands: 20 to <30 kg, 375/50 mg twice a day (20 patients); 30 to <40 kg, 450/60 mg twice a day (24 patients); =40 kg, 600/100 mg twice a day (36 patients). With optmised background therapy.

80 children and adolescents (71% male; median age of 14) received DRV/r in this study. Mean baseline viral load was 4.64 log10 (SD=/-0.80) copies/mL, median baseline CD4 count was 330 (range 6-1505; 31% had CD4 <200) cells/mm3, and CD4 percentage was 17% (range 0.7-47).

Median number of previously used antiretrovirals was 9 (range 3-13). Median baseline of 3 (range 0-6) International AIDS Society (IAS) -USA primary protease inhibitor (PI) mutations, 11(0-19) PI resistance-associated mutations (RAM; 65% had =10 PI RAM) and 1 NNRTI and 4 NRTI RAM.

The investigators reported that the target DRV pharmacokinetic exposures for treatment-experienced adults were achieved across all age groups and weight bands.

71 patients (89%) reported 1 adverse event. The most common (>10% of patients) were upper respiratory tract infection, cough, pyrexia, vomiting, diarrhea, and lymphadenopathy. Most adverse events were grade 1 or 2. Grade 3 or 4 adverse events were reported in 18 patients (23%); most were single events in individuals and were considered unrelated to DRV/r. Serious adverse events were reported in 9 patients (11%). No deaths were reported during treatment period. One patient permanently discontinued treatment due to grade 3 anxiety, considered to be unrelated to DRV/r by the investigator.

At week 24, 74% of patients had a viral load reduction of =1.0 log10 from baseline. Viral load <400 copies/mL and <50 copies/mL were achieved by 64% and 50% of patients, respectively. The mean increase in CD4 cell count from baseline was 117 cells/mm3.

The investigators concluded: DRV/r was an effective treatment in treatment-experienced HIV-1-infected pediatric patients (6 to 17 years) due to the favorable tolerability and pharmacokinetics profiles, and virologic response rates at week 24.

Comment

The optimised background therapy in this study did not permit the use of TMC125 (etravirine) or integrase inhibitors. T20 was allowed and it would be helpful to know how much this contributed to achieving virological suppression.

Frankly, we need to do better than 50% of patients achieving <50 copies/mL, although the ITT outcomes at Week 48 are still pending.

Bologna R, Rugina S, Cahn P et al. Safety and efficacy of darunavir co-administered with low-dose ritonavir in treatment-experienced children and adolescents at week 24. 15th CROI. February 2008. Boston, MA, USA. Oral abstract 78LB.