Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects.
OBJECTIVE
The purpose of this work was to obtain long-term safety and efficacy data for antiretroviral regimens containing emtricitabine in HIV-infected pediatric subjects and confirm that a pediatric dose of 6 mg/kg once daily would provide steady-state emtricitabine concentrations comparable to those observed in adults given 200 mg of emtricitabine once daily.


METHODS
HIV-infected subjects between 3 months and 16 years of age were enrolled, including 71 antiretroviral-naïve subjects and 45 antiretroviral-experienced subjects. Naive subjects received emtricitabine plus stavudine plus lopinavir or ritonavir. Experienced subjects replaced the lamivudine in their existing regimens with emtricitabine. Tolerance, safety, disease progression, and virologic and immunologic responses were evaluated.


RESULTS
The Kaplan-Meier probability of persistent virologic response in the intent-to-treat population through week 164 at < or = 400 copies per mL and < or = 50 copies per mL was 74% and 62%, respectively. Three subjects (3%) discontinued the study for adverse events, 8 (7%) for virologic failure, and 1 died through a median follow-up of 164 weeks. The annualized incidence rate of grade 3 to 4 adverse events and grade 3 to 4 laboratory abnormalities was 6% and 3%, respectively. The annualized incidence rate of serious adverse events was 9%, with 1% attributed as related to emtricitabine. Genotypic analysis showed the emergence of the M184V mutation in 4 of the 15 subjects who experienced virologic failure through week 164. Pharmacokinetic evaluation demonstrated plasma drug exposures in these children comparable to adults receiving the approved dose of 200 mg once daily.


CONCLUSIONS
These results demonstrate the safety and efficacy of emtricitabine in pediatric patients. They also support that the safety and efficacy profile of emtricitabine in children is similar to that demonstrated in adults.
Saez-Llorens
Xavier
X
Infectious Disease Department, Hospital del Nino, Panama City, Panama.
Violari
Avy
A
Ndiweni
Dalubuhle
D
Yogev
Ram
R
Cashat
Miguel
M
Wiznia
Andrew
A
Chittick
Greg
G
Harris
Jeanette
J
Hinkle
John
J
Blum
M Robert
MR
Adda
Nathalie
N
Rousseau
Franck
F
D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008134:Long-Term Care; D008297:Male; D015999:Multivariate Analysis; D010349:Patient Compliance / Q000706:statistics & numerical data*; D011446:Prospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D016896:Treatment Outcome
D003841:Deoxycytidine; D000068679:Emtricitabine