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Safety and Efficacy of Raltegravir in Pediatric HIV Infection. Preliminary Analysis from the International Maternal Pediatric Adolescent AIDS Clinical Trials Group, P1066
Andrew Wiznia*1, P Samson2, E Acosta3, H Teppler4, E Sheeran5, B Graham6, T Fenton2, E Handelsman7, C Worrell8, S Nachman9, and IMPAACT P1066
1Jacobi Med Ctr, Albert Einstein Coll of Med, Bronx, NY, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Univ of Alabama at Birmingham, US; 4Merck Res Labs, North Wales, PA, US; 5Social & Sci Systems Inc, Silver Spring, MD, US; 6Frontier Sci & Tech Res Fndn, Amherst, NY, US; 7NIAID, NIH, Bethesda, MD, US; 8Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; and 9State Univ of New York at Stony Brook, US
Background: Raltegravir (RAL) is a potent and
selective HIV-1 integrase inhibitor approved for use in adults. IMPAACT P1066,
the first RAL pediatric trial, is an ongoing prospective, non-randomized, open
label, dose finding trial of RAL plus optimized background regimen (OBR) in
treatment experienced children.
Methods: To date, children ages ≥12 to <19 (cohort
I) and ≥6 to <12 (cohort II) have enrolled, sequentially older to
younger. In stage 1, RAL poloxamer film tablets were added to a stable, failing
ART regimen; pharmacokinetics was done on day 7 to 12 and then OBR started.
Clinical and lab safety and efficacy evaluations were routinely performed.
Results: To date, 32 patients have accrued: 22 in Cohort
1 and 10 in cohort II. Participants were initially treated at 6 or 8 mg/kg/dose
twice daily with a maximum dose of 600 mg twice daily; cohort II received 8
mg/kg twice daily. The patients were: 47% male, 66% black, and 25% white. Median
baseline HIV-1 RNA was 4.44 log10 copies/mL and were similar between
the 2 cohorts. Median CD4% was 20 (0 to 42%). Of the 5 participants who had ≥grade
3 adverse event, 4 had neutropenia, 1 increased lipids, and 1 increased
creatinine associated with aminoglycoside use; only 1 neutropenia was judged to
possibly related to RAL. There were no deaths; the only 2 withdrawals were due
to poor adherence. In an intent-to-treat analysis of those treated at 8 mg/kg
and scheduled to reach week 8 or 12 prior to August 24, 2008 and where off-treatment
was considered a failure, HIV RNA <400 copies/mL was achieved in 14 of 18
(78%) and 12 of 14 (86%) at weeks 8 and 12, respectively. Median CD4% was 24%
at both weeks 8 and 12.
Conclusions: Preliminary, short-term and partial data
from IMPAACT P1066 suggests that RAL + OBR in children ages 6 to 18 was generally
safe, well tolerated and effective. Enrollment into these cohorts, as well as
use of a chewable formulation for children <12 years of age, is continuing.
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