Study TMC114-C212 is an ongoing 48-week,
open-label, Phase 2 study evaluating pharmacokinetics, safety, tolerability, and
efficacy in 80 treatment-experienced HIV-infected children
and adolescent aged 6 to 17 years. Most (71%) were male and the median age
was 14 years.
The mean baseline viral load was 4.64 log10 copies/mL, the
median baseline CD4 count was 330
cells/mm3, and the median CD4 percentage was 17%; about one-third had fewer than
200 cell/mm3. Participants had used a median of 9 previous antiretroviral drugs
and had multiple viral drug-resistance mutations.
In part 1 of the study,
patients were randomly assigned to 1 of 2 darunavir/ritonavir
dose groups. In the second part, all participants received the recommended dose
per body weight:
•
40 kg or more: 600/100 mg twice-daily (36 patients).
Assessments
for pharmacokinetic, safety, and efficacy parameters were performed throughout
the study. Primary 24-week safety and efficacy data from part 2 were presented
at CROI. Results
•
The target darunavir pharmacokinetic exposures for treatment-experienced adults
were achieved across all pediatric age groups and weight bands, confirming appropriate
dose selection in this population.
•
At week 24, 74% of patients had a confirmed virological response, defined as HIV
RNA reduction of at least 1.0 log10 copies from baseline.
•
64% achieved HIV RNA < 400 copies/mL and 50% viral load < 50 copies/mL.
•
The mean 24-week increase in CD4 count from baseline was 117 cells/mm3.
•
71 children (89%) reported at least 1 adverse event.
•
The most common treatment-emergent adverse events (occurring in more than 10%
of patients) were upper respiratory tract infections, cough, fever, vomiting,
diarrhea, and lymphadenopathy (swollen lymph nodes).
•
Most adverse events were mild-to-moderate (Grade 1 or 2) in severity.
•
Most of these occurred as single events in individual patients, and were deemed
unrelated to darunavir/ritonavir.
•
1 child permanently discontinued treatment due to Grade 3 anxiety, which the investigator
considered unrelated to darunavir/ritonavir.
•
No deaths occurred during treatment.
Conclusion
Based
on these interim finding, the researchers concluded, "Darunavir/ritonavir
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."
Hosp de Pediatria JP
Garrahan, Buenos Aires, Argentina; Spitalul Clinic de Boli Infectioase, Constanta,
Romania; Fndn Huesped, Buenos Aires, Argentina; St. Jude Children's Research Hospital,
Memphis, TN; Hosp Necker-Enfants Malades, Paris, France; Tibotec, Inc, Mechelen,
Belgium.
3/07/08
Reference R
Bologna, S Rugina, P Cahn, and others. Safety and Efficacy of Darunavir Co-administered
with Low-dose Ritonavir in Treatment-experienced Children and Adolescents at Week
24. 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008).
Boston, MA. February 3-6, 2008. Abstract 78LB.
Boosted
Darunavir (Prezista) Is Safe and Effective for Children with HIV 
Results
