Published online March 10, 2008
PEDIATRICS Vol. 121 No. 4 April 2008, pp. e827-e835 (doi:10.1542/peds.2006-3078)

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Saez-Llorens, X. Search for Related Content PubMed PubMed Citation Articles by Saez-Llorens, X. Related Collections Infectious Disease & Immunity Social Bookmarking                         What's this?

ARTICLE

Long-term Safety and Efficacy Results of Once-Daily Emtricitabine-Based Highly Active Antiretroviral Therapy Regimens in Human Immunodeficiency Virus-Infected Pediatric Subjects

Xavier Saez-Llorens, MD^a, Avy Violari, MD^b, Dalubuhle Ndiweni, MD^c, Ram Yogev, MD^d, Miguel Cashat, MD^e, Andrew Wiznia, MD^f, Greg Chittick, BSc^g, Jeanette Harris, BS^g, John Hinkle, PhD^g, M. Robert Blum, PhD^g, Nathalie Adda, MD^g, Franck Rousseau, MD^g for the FTC-203 Study Team

^a Infectious Disease Department, Hospital del Nino, Panama City, Panama
^b Perinatal HIV Research Unit, Baragwanath Hospital, Soweto, South Africa
^c Pediatric HIV Clinic, Helen Joseph Hospital, Johannesburg, South Africa
^d Section of Pediatric and Maternal HIV Infection, Children's Memorial Hospital, Chicago, Illinois
^e Department of Infectious Diseases, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
^f Division of Pediatric Allergy and Immunology, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York
^g Gilead Sciences, Inc, Durham, North Carolina

OBJECTIVES. 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.

PATIENTS AND 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 400 copies per mL and 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.

---

Key Words: emtricitabine • FTC • pediatric • HIV • pharmacokinetics

Abbreviations: QD—once daily • ART—antiretroviral therapy • PCR—polymerase chain reaction • AUC—area under the plasma concentration-time curve over the 24 hour dosing interval • BID—twice daily • TLOVR—time to loss of virologic response • AIR—annualized incidence rate • SAE—serious adverse event

---

Accepted Aug 20, 2007.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?