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PACTG Protocol 1021: A Phase I/II Study of a Once-daily Regimen of Emtricitabine, Didanosine, and Efavirenz in HIV-infected, Therapy-naïve Children and Adolescents
Mobeen Rathore*1, R McKinney2, C Hu3, P Britto3, M Smith4, L Serchuck5, L Draper6, A Horga7, G Chittick8, A Weinberg9, and P1021 Study Team
1Univ of Florida, Jacksonville, US; 2Duke Univ, Durham, NC, US; 3Harvard Univ, Boston, MA, US; 4NIH, Bethesda, MD, US; 5Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; 6Frontier Sci and Tech Res Fndn, Amherst, NY, US; 7Bristol-Myers Squibb R&D, Wallingford, CT, US; 8Gilead Sci, Foster City CA, US; and 9Univ of Colorado Hlth Sci Ctr, Denver, US
Background: Compliance with complex ART 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 once-daily regimen of 3 antiretroviral drugs—emtricitabine
(FTC), didanosine (ddI), and efavirenz (EFV)—was tested in 37 therapy-nave HIV-infected
children and adolescents between 3 and 21 years of age (inclusive). Subjects
were followed for at least 96 weeks on an intent-to-treat basis. Signs, symptoms,
plasma HIV-1 RNA viral load, CD4 counts, and safety laboratories were followed
regularly. Endpoints were the proportion of subjects with plasma HIV <400 or
50 HIV copies/mL, and safety and tolerability of the regimen.
Results: We enrolled 37 subjects at 16 sites. There were no
deaths, 2 withdrew because of rash within the first 2 weeks of study, and 25
(68%) completed 144 weeks of the study. There were 4 grade-4 (low glucose = 2
and high gamma glutamyl transferase [GGT] = 2) and 7 grade-3 episodes judged
possibly drug related. At week 144, of the 37subjects 25 (68%) achieved viral
suppression to <400 RNA copies/mL, and 24 (65%) were maintaining sustained
suppression at <50 copies/mL. The median baseline CD4 count was 310/l (17%),
which increased at week 144 by a median +308 cells/l and +16% CD4, p
<0.0001 for both. Pharmacokinetic results were as predicted for FTC and ddI,
while EFV concentrations in children receiving EFV oral solution were lower
than anticipated, requiring a dose escalation after the initial planned
assessment point.
Conclusions: A once-daily regimen of FTC, ddI, and EFV
proved to be safe and effective in this 37 subject, multi-year phase I/II
study. By intent-to-treat analysis, 65% of subjects demonstrated sustained HIV
viral load suppression to <50 copies/mL through week 144.
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