Download PACTG 1021 CROI 2006 Final

Phase I-II Study of a Once-Daily Regimen of Emtricitabine, Didanosine, and
Efavirenz in HIV-infected, Therapy Naïve Children and Adolescents (PACTG
Protocol 1021)
Authors: McKinney, R., Rathore, M., Hu, C., Britto, P., Smith, M., Serchuck, L.,
Rodman, J., Draper, L., Reynolds, L., Chittick, G., and the Pediatric ACTG Protocol
1021 Team
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 once-daily regimen of three
antiretroviral drugs, emtricitabine (FTC), didanosine (ddI), and efavirenz (EFV), was
tested in 37 therapy-naïve 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 below 400 or 50 HIV copies/ml, and safety and tolerability of the regimen.
Results 37 subjects enrolled at 16 sites. Two rashes during the first two weeks of therapy
were the only adverse events leading to study drug discontinuation Early study
discontinuations included 2 incarcerations, one international move, two refusals for
follow up, and two viral failures on treatment. One grade 4 (low glucose) and 3 grade 3
adverse events judged possibly drug related occurred. There were no deaths. Virologic
outcomes showed promise, with 32/37 (85%) subjects achieving viral suppression to
< 400 RNA copies per ml, and 26/37 (72%) subjects maintaining sustained suppression at
< 50 copies/ml through week 96 (See Figure). The median baseline CD4 count was
310/µl (17%), which increased at Week 96 by a median +329 cells/µl (by +18% CD4).
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, two year Phase III study. By ITT analysis, 72% of subjects demonstrated sustained HIV viral load
suppression to <50 copies/ml through week 96.
Proportion <400 or <50 HIV-1 Copies per ml by study week
1
P 0.9
r 0.8
o 0.7
p
0.6
o
0.5
r
t 0.4
<400
<50
i 0.3
o 0.2
n 0.1
0
0
12
24
36
48
60
72
84
96
Week
McKinney R, Rathore M, Hu C, Britto P, Smith M, Serchuck L, et al. Phase I-II study of a once-daily regimen of
emtricitabine, didanosine, and efavirenz in HIV-infected, therapy naive children and adolescents (PACTG Protocol 1021)
[abstract]. 13th Conference on Retroviruses and Opportunistic Infections (CROI); 2006 February 5-9; Denver, Colo, USA.