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

• Published in: Pediatrics (Evanston) Vol. 120; no. 2; p. e416
• Main Authors: McKinney, Jr, Ross E, Rodman, John, Hu, Chengcheng, Britto, Paula, Hughes, Michael, Smith, Mary Elizabeth, Serchuck, Leslie K, Kraimer, Joyce, Ortiz, Alberto A, Flynn, Patricia, Yogev, Ram, Spector, Stephen, Draper, Linda, Tran, Paul, Scites, Melissa, Dickover, Ruth, Weinberg, Adriana, Cunningham, Coleen, Abrams, Elaine, Blum, M Robert, Chittick, Gregory E, Reynolds, Laurie, Rathore, Mobeen
• Format: Journal Article
• Language: English
• Published: United States 01.08.2007
• Subjects: Adolescent; Adult; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Child; Child, Preschool; Clinical Protocols; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Didanosine - administration & dosage; Didanosine - adverse effects; Drug Administration Schedule; Emtricitabine; Female; Follow-Up Studies; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV-1 - drug effects; Humans; Male; Time
• ISSN: 1098-4275
• DOI: 10.1542/peds.2006-0925

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. 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 > or = 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. 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 microL (17%), which increased at week 96 by a median of +329 cells per microL (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. 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.