CROI: Darunavir found effective and tolerable in treatment-experienced children and adolescents at 24 weeks

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Week 24 results from a study of darunavir (Prezista) in a treatment experienced, HIV-infected pediatric population have shown the drug to be virologically effective and generally well tolerated, with a pharmacokinetic profile comparable to that in treatment-experienced adults.

The late-breaker results were presented to the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston on Tuesday by Sabrina Spinoza-Guzman of Tibotec on behalf of a multinational study group.

TMC114-C212 is an ongoing open-label study of ritonavir-boosted darunavir (DRV/r) in antiretroviral-experienced children and adolescents, otherwise known as the DELPHI (Darunavir EvaLuation in Pediatric HIV-1-Infected treatment-experienced patients) trial. In part I, patients were randomised to one of two DRV/r dose groups. In part II, presented here, all patients received the recommended dose per body weight, as described below. Safety, tolerability, and efficacy data from week 24 of this 48-week study were presented at the Tuesday oral session.



A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.


Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


Of or relating to children.

All 80 study participants were aged 6 to 17 years, and had been on HAART for at least 12 weeks. All received an optimised background regimen of at least two antiretroviral agents. In addition, DRV/r dosages were assigned based on body weight. Twenty patients weighing from 20 to

Twenty-four patients weighing from 30 to

Median age at baseline was 14 years. Fifty-seven participants (71%) were male. At baseline, mean HIV viral load was 4.64 log10 copies/mL, median CD4 count was 330 cells/mm3 (range, 6 to 1505), and CD4 percentage was 17% (range, 0.7 to 47). CD4 counts were 3 in 31% of the participants. Participants were heavily treatment-experienced, with a median of nine ARVs having previously been used (range, 3 to 19), and a median baseline of 4 NRTI resistance-associated mutations (RAMs), 1 NNRTI RAM, 11 PI RAMs (65% had ≥10 PI RAMs), and 3 primary protease inhibitor (PI) mutations as defined by the International AIDS Society-USA (IAS-USA).

At week 24, viral load had decreased to below 50 copies/ml in 50% of the study participants, and below 400 copies/mL in 64%. A reduction of at least 1 log10 in viral load was achieved by 74%. The mean increase in CD4 cell count from baseline was 117 cells/mm3.

At least one adverse event (AE) was reported by 71 participants (89%). The most common, occurring in over 10% of participants, were upper respiratory tract infection, cough, pyrexia, vomiting, diarrhea, and lymphadenopathy. Most AEs were grade 1 or 2 in severity; grade 3 or 4 adverse events were reported in 18 patients (23%). Serious adverse events were reported by 9 (11%) of the participants and were all single events. There were no deaths during the 24-week period and only one participant withdrew from the study due to an AE (grade 3 anxiety that the investigator considered to be unrelated to the study drug).

Targeted darunavir pharmacokinetic exposures for treatment-experienced adults were reached in all weight bands and age groups. 24-hour AUC and trough concentrations (C0h) were very close to those found in adults in the POWER1 and 2 studies; trough concentrations (mean, 3888 ng/ml, range 1836 – 7821) were well above the corrected EC50 value of 550 ng/ml in all children.

The investigators concluded that ritonavir-boosted darunavir showed good virologic response rates, positive clinical outcomes, favourable safety and tolerability, and comparable exposure to adults in this group of treatment-experienced children and adolescents at week 24.


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.