Background:  Raltegravir (RAL) is a potent selective HIV-1 integrase inhibitor approved for use in adults. P1066 is a study of open label RAL in treatment experienced HIV⁺ youth. PK, safety, and efficacy data in HIV⁺ youth 12 to 18 year-old (cohort I) were recently reported. Here we report PK, 12 week (wk) antiretroviral activity and all available safety data through 14 September, 2009 from cohort IIA, 6 to 11 year-old participants placed on RAL tablets. 

Methods:  HIV⁺ youth enrolled in Stage 1: dose finding with intensive PK, safety and wk 12 efficacy. Entry criteria included HIV RNA>1000 copies/mL, treatment experienced but naïve to integrase inhibitors, and excluded patients (pt) with HBV or HCV. Intensive PK were completed between days 5 and 12. ARV were optimized after intensive PK studies completed. After PK studies were examined, a dose for continued study was selected. Success was defined as achieving and maintaining >1-log drops from baseline or viral loads of <400 copies/mL and on-study treatment at study specified dose at week 12. Any patient taken off-treatment prior to week 12 was considered a failure. Patients with vRNA <50 were also examined. All patients were included in the safety analyses. 

Results:  Baseline demographics: Male: 60%; Race: 90% Black/African American, Median: weight = 30 kg; age = 9 years; log₁₀RNA = 4.4, CD4 = 536. Efficacy (Intent-to-Treat) data is available on 8 patients. Subjects dosed at 8 mg/kg (200, 300, or 400 mg) showed a geometric mean (GM) AUC ₁₂ of 14.8 mMxh (2.3 to 111) allowing for selection of 400 mg twice daily of adult formulation tablets as a final dose. Subjects weighing < 25kg were placed on alternative formulations. Repeat PK were done on all subjects at 400 mg twice daily which revealed a GM AUC ₁₂ of 15.8 mMxh (1.6 to 111). At 400 mg twice daily the GM trough and C_max were 246 nM and 4.8 mM. There were 3 grade 3 adverse events, 1 possibly related (low ANC). No treatment discontinuations were due to adverse events. At 12 weeks, 75% achieved success, 95%CI 35%, to 97%; 62% achieved <50 copies/mL, 95%CI 24% to 91%. Median point change from baseline: CD4%: 2.5, 95%CI -1 to 8; CD4 count: 86, 95%CI 60 to 219. Success was similar to previously reported data on the 12 to 18-year old study cohort.

Conclusions: A RAL dose of 400 mg twice daily of the adult formulation was chosen for continued study in HIV infected youth ages 6 to 11 years and at least 25 kg in weight. In these subjects, RAL appears generally safe and well tolerated through week 12, and achieved efficacy rates comparable to those in treatment experienced youth aged 12 to 18 years and adults.