Abstract 270 / Session 38
Evidence of Potent Antiviral Activity in a Phase l/ll Study of Nefinavir Mesylate (Viracept) in HIV Infected Chidlren.ÿÿÿ
P KROGSTAD (1)*, A WIZNIA (2), K LUZURIAGA (3), W DANKNER (4), K NIELSEN (1), B KERR (5), A HENDRICKS (5), M. GERSTEN (5), B. BOCZANY (5), S SPECTOR (3), AND Y BRYSON (1). (1) Univ. of California at Los Angeles, CA; (2) Bronx Lebanon Hospital, Bronx, NY; (3) Univ. of Massachusetts, Worcester, MA; (4) Univ. of California at San Diego, CA; (5) Agouron Pharm, Inc., La Jolla, CA.
ÿÿÿ Sixty HIV infected infants and children ranging from 3 mo to 13 yrs of age (median 5.4 yrs) received nelfinavir (NFV) to
evaluate the pharmacokinetics, tolerance and potential efficacy of the drug when used in combination with nucleoside reverse
transcriptase inhibitors (NRTI). A dose of 20 mg/kg to 30 mg/kg thrice daily yielded steady state plasma NFV levels comparable to those
seen in adults during Phase II/III trials. In a subset of older children, NFV plasma levels were found to be similar for the NFV
oral powder and tablet formulations. NFV was well tolerated: three patients reported transient Grade 2 diarrhea (resulting in
study discontinuation by one). Other Grade 2 or greater clinical events considered to be possibly related to NFV included rash or
fever in one patient each. The mean baseline HIV plasma RNA (Roche Amplicor HIV Monitor) was 4 X104copies/ml). By 10 weeks of
study, median viral RNA decreased by 1.3 log for the cohort as a whole. The decline in RNA load was greatest and best sustained in
children who had >1 NRTI added within six weeks of starting NFV compared to those having only NFV added to their treatment
regimen. At 34 weeks of followup, plasma HIV RNA was undetectable in 10/18 (55%), including 8 of 11 (73%) subjects receiving NFV with
>1 new NRTI. Children with undetectable viral RNA at 34 weeks of followup had a higher median % CD4+ lymphocyte increase over
baseline than those with detectable viremia. (8.5% versus 4.6%) These data indicate that nelfinavir has a predictable and safe
profile in children and infants. In addition, improved and sustained suppression of HIV is most readily achieved when nelfinavir is
combined with one or more new antiretroviral agents. |
