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.
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 > 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.


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 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.


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.
McKinney
Ross E
RE
Department of Pediatrics, Duke University Medical Center, Box 3461, Durham, NC 27710, USA. ross.mckinney@duke.edu
Rodman
John
J
Hu
Chengcheng
C
Britto
Paula
P
Hughes
Michael
M
Smith
Mary Elizabeth
ME
Serchuck
Leslie K
LK
Kraimer
Joyce
J
Ortiz
Alberto A
AA
Flynn
Patricia
P
Yogev
Ram
R
Spector
Stephen
S
Draper
Linda
L
Tran
Paul
P
Scites
Melissa
M
Dickover
Ruth
R
Weinberg
Adriana
A
Cunningham
Coleen
C
Abrams
Elaine
E
Blum
M Robert
MR
Chittick
Gregory E
GE
Reynolds
Laurie
L
Rathore
Mobeen
M
D000293:Adolescent; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016049:Didanosine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D013995:Time
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D000068679:Emtricitabine; C098320:efavirenz; D016049:Didanosine