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Treatment Responses to Atazanavir-containing HAART in a Drug-naïve Pediatric Population in South Africa
T Meyers1, R Rutstein2, P Samson3, A Violari1, Megan Palmer*1, J Kiser4, C Fletcher4, B Graham5, M Horga6, G Aldrovandi7, and PACTG 1020A Study Team
1Chris Hani Baragwanath Hosp, Johannesburg, South Africa; 2Children`s Hosp of Philadelphia, PA, US; 3Frontier Sci and Tech Res Fndn, Harvard Sch of Publ Hlth, Boston, MA, US; 4Univ of Colorado, Denver, US; 5Frontier Sci and Tech Res Fndn, Amherst, NY, US; 6Bristol-Myers Squibb, Wallingford, CT, US; and 7Children`s Hosp of Los Angeles, CA, US
Background: Pediatric AIDS Clinical Trials Group (PACTG)
1020A is a phase I/II study of atazanavir (ATV)±ritonavir (r) with 2 NRTI
(excluding tenofovir [TDF]) in HIV-infected children (91 days to 21 years) in
the United States and South Africa. This report presents data from the
treatment-naïve South African children who participated in the dose-finding
study, for age (<2 years, 2 to 13 years, >13 years) and formulation
(powder vs capsule) cohorts.
Methods: ATV dosing started at 310 mg/m2 for each cohort and
was adjusted based on day 7 24-hour, intensive pharmacokinetic and week 4
safety. Cohort dose acceptance criteria were: AUC ≥30 µg*hour/mL and C24
≥60 ng/mL in 4 of 5 patients; no AUC <15 µg*hour/mL; and median AUC
for 5 patients ≤60 µg*hour/mL and ≤1 of 5 patients with ≥
grade 3 adverse events, none life-threatening. Based on pharmacokinetic and
safety criteria, either 5 additional patients were enrolled at that dose or the
starting dose was altered. An optimal dose was based on ≥10 evaluable patients
with acceptable pharmacokinetic and safety results.
Results: We have enrolled 183 patients, 62 from South Africa. We report 48-week treatment outcomes for 57 treatment-naïve South African
children (ATV–r = 22, ATV+r = 35); 29 were female. At baseline, median age, 6 years
(91 days to 21 years); CD4 count, 411 (24 to 2192); CD4%, 13% (1 to 35); log10
viral load, 5.0 (3.6 to 5); and mean height z-score, –2.09 (–4.56 to 0.73) and
weight z-score, –1.98 (–5.80 to 0.91). In an intent-to-treat analysis, 35 of 48
(73%, 95%CI 58% to 85%) had viral load <400 by 48 weeks. Weight and height
z-score improved significantly at week 48; mean change in height z-score +0.27
(p = 0.04 t-test) and mean change in weight z-score +0.79 (p <0.0001
t-test). Of the 11 patients who discontinued ATV, 5 did so because of
toxicity (hyperbilirubinemia, LFT increase, or QT interval changes), 1 due to
death (unrelated), and 5 for other reasons (e.g., lost to follow-up, need for
protocol disallowed medications).
Conclusions: Treatment-naïve children
in South Africa respond well to HAART with once-daily ATV±r with an acceptable
safety profile, improved growth parameters, and virologic suppression.
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