Children

The US Food and Drug Administration approved the new 75mg darunavir (Prezista) tablet for use by children aged between six and 18 years. Ritonavir-boosted darunavir is approved for twice-daily dosing in combination with other anti-HIV drugs. Dosing is determined by the child’s weight; the minimum weight required for treatment with darunavir/ritonavir is 20kg.

For children weighing 20-30kg the twice-daily dose of darunavir/ritonavir is 375/50mg. Children whose weight is between 30-40kg should receive twice-daily doses of darunavir/ritonavir of 450/60mg. Children weighing over 40kg would use the adult dosing of darunavir/ritonavir at 600/100mg twice a day. Darunavir should not be used to treat HIV-positive children aged under three, and the safety and efficacy of the drug in children aged between three and six years has not been established.

Week 24 results from the DELPHI (Darunavir EvaLuation in Paediatric HIV-1-Infected treatment-experienced patients) trial reported that the drug was virologically effective and generally well tolerated in children, with a pharmacokinetic profile comparable to that in treatment-experienced adults.1 The 48-week final results confirm those findings.2

DELPHI (also known as TMC114-C212) was an ongoing, 48-week open-label study of ritonavir-boosted darunavir DRV/r). The 80 study participants were aged 6 to 17 years and had been on HAART for at least 12 weeks at baseline. The median baseline viral load was ~40,000 copies/ml and median CD4 cell count was 330 cells/mm3. All received an optimised background regimen of at least two antiretroviral agents. DRV/r dosages were assigned based on body weight.

Following 48 weeks of treatment, 65% of the participants had a one log viral load drop (vs 74% at 24 weeks), Viral load was below 400 copies/ml in 59% (vs 64% at 24 weeks) and >50 copies/ml in 48% (50% at 24 weeks).

Viral load below 50 copies/ml was achieved in 59% of those with no pre-existing darunavir-associated mutations, 47% of those with 1 or 2 mutations, and in none of the participants who entered the study with three or more mutations. Inadequate background therapy (no use of enfuvirtide) was suggested as one of the possible reasons for this resistance barrier, lower than what has been seen in adults (but with comparable DRV exposure levels). The mean increase in CD4 cell count from baseline was 147 cells/mm3 (vs 117 at 24 weeks).

A grade 3 and 4 adverse event occurred in 28%, but there were no deaths. Frequent health problems were fever, cough, upper respiratory tract infections, and diarrhoea. Significant laboratory values included neutropenia (13%), increased liver enzymes and amylase (11% each), and increased lipase (4%). Lipid values were lower than at baseline, with triglycerides below normal.

References

  1. Bologna R et al. Safety and efficacy of darunavir co-administered with low-dose ritonavir in treatment-experienced children and adolescents at Week 24. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, Abstract 78LB, 2008
  2. Blanche S et al. 48-week safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents in DELPHI. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H-894, Washington, 2008