Published online July 23, 2007
PEDIATRICS Vol. 120 No. 2 August 2007, pp. e416-e423 (doi:10.1542/peds.2006-0925)

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ARTICLE

Long-term Safety and Efficacy of a Once-Daily Regimen of Emtricitabine, Didanosine, and Efavirenz in HIV-Infected, Therapy-Naive Children and Adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021

Ross E. McKinney, Jr, MD^a, John Rodman, PharmD^b,, Chengcheng Hu, PhD^c, Paula Britto, MS^c, Michael Hughes, PhD^c, Mary Elizabeth Smith, MD^d, Leslie K. Serchuck, MD^e, Joyce Kraimer, MS^f, Alberto A. Ortiz, MS^f, Patricia Flynn, MD^b, Ram Yogev, MD^g, Stephen Spector, MD^h, Linda Draper, BAⁱ, Paul Tran, RPh^d, Melissa Scites, RN^j, Ruth Dickover, PhD^k, Adriana Weinberg, MD^l, Coleen Cunningham, MD^m, Elaine Abrams, MDⁿ, M. Robert Blum, PhD^o, Gregory E. Chittick, BSc^o, Laurie Reynolds, BA^p, Mobeen Rathore, MD^j for the Pediatric AIDS Clinical Trials Group Protocol P1021 Study Team

^a Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
^b Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee
^c Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
^d Division of AIDS, National Institute of Allergy and Infectious Diseases
^e Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
^f Social & Scientific Systems, Inc, Silver Spring, Maryland
^g Department of Pediatrics, Children's Memorial Hospital, Chicago, Illinois
^h Department of Pediatrics, University of California, San Diego, California
ⁱ Frontier Science and Technology Research Foundation, Amherst, New York
^j Department of Pediatrics, University of Florida Health Science Center, Jacksonville, Florida
^k Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
^l Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado
^m Department of Pediatrics, State University of New York Health Science Center, Syracuse, New York
ⁿ Department of Pediatrics, Harlem Hospital, New York, New York
^o Gilead Sciences, Inc, Durham, North Carolina
^p Bristol-Myers Squibb Company, Wallingford, Connecticut

BACKGROUND. Compliance with complex antiretroviral therapy regimens is a problem for HIV-1–infected children and their families. Simple, safe, and effective regimens are important for long-term therapeutic success.

METHODS. A novel, once-daily dosing regimen of 3 antiretroviral drugs, emtricitabine, didanosine, and efavirenz, was tested in 37 therapy-naive HIV-infected children and adolescents between 3 and 21 years of age (inclusive). Subjects were followed for 96 weeks on an intention-to-treat basis. Signs, symptoms, plasma HIV-1 RNA viral load, CD4 counts, and safety laboratories were followed regularly. End points were the proportion of subjects with plasma HIV <400 or 50 HIV copies per mL and safety and tolerability of the regimen.

RESULTS. Thirty-seven subjects enrolled at 16 sites. Two subjects with rashes during the first 2 weeks of therapy were the only adverse events leading to study-drug discontinuation. Other early (before protocol-scheduled conclusion) study discontinuations included 3 viral failures on treatment and 5 patients who stopped therapy for apparently nonmedical reasons. Possible drug-related adverse events included 1 grade 4 low-glucose and 5 varied grade 3 events. There were no deaths. Virologic outcomes demonstrated that 32 (85%) of 37 subjects achieved viral suppression to <400 RNA copies per mL, and 26 (72%) of 37 subjects maintained sustained suppression at <50 copies per mL through week 96. The median baseline CD4 count was 310 per µL (17%), which increased at week 96 by a median of +329 cells per µL (by +18% CD4). Pharmacokinetic results were as predicted for emtricitabine, didanosine, and efavirenz capsules, whereas efavirenz concentrations in children receiving efavirenz oral solution were lower than anticipated, requiring a dose escalation after the planned assessment point.

CONCLUSIONS. A once-daily regimen of emtricitabine, didanosine, and efavirenz proved to be safe and tolerable and demonstrated good immunologic and virologic efficacy in this 2-year study.

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Key Words: agents • antiretroviral • AIDS • child • didanosine • efavirenz • emtricitabine • HIV

Abbreviations: AUC—area under the curve • CI—confidence interval

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Accepted Jan 26, 2007.

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