Use of Raltegravir in Pediatric HIV-1 Infection

Marcia L. Buck, Pharm.D., FCCP, FPPAG; Kristi N. Hofer, Pharm.D; Michelle W. McCarthy, Pharm.D.; FASHP Susan B. Cogut, Pharm.D

Disclosures

Pediatr Pharm. 2012;18(1) 

In This Article

Clinical Studies

The approval of raltegravir in pediatric patients was based on the results of a Phase I/II multicenter open-label dose-finding trial in 126 children with HIV-1 infection.[3] The IMPAACT P1066 study was designed to evaluate the safety and efficacy of raltegravir in children between 2 and 18 years of age. As described earlier, dosing was based on patient age and weight.

Ninety-six of the study participants were included in the clinical assessment. The median age of these patients was 13 years. At baseline, they had a mean plasma HIV-1 RNA of 4.3 log10copies/mL, a median CD4 count of 481 cells/mm3 (range 0–2361 cells/mm3), and a median CD4% of 23.3% (range 0–44%). Most patients had previously received treatment, with 78% having taken at least one NNRTI and 83% having taken at least one PI. Ninety-three children completed the 24-week treatment period. Three patients were excluded because of non-adherence. At the completion of the study, 54% of the children had an HIV-1 RNA < 50 copies/mL and 72% had achieved an HIV-1 RNA decrease of at least 1 log10copies/mL from baseline. The mean increase in CD4 count from baseline was 199 cells/mm3, or 3.8%. These results were similar to those reported in the two Phase III studies conducted by the manufacturer in adults (BENCHMRK 1 and BENCHMRK 2).[3]

Other evidence of the efficacy of raltegravir comes from the French Expanded Access Program.[7,8] In 2009, Thuret and colleagues from the Service d'Hématologie Pédiatrique described the use of combination therapy with raltegravir, darunavir, and etravirine in 12 adolescents from 12 to 17 years of age with multidrug-resistant HIV-1 infection.[7] At follow-up (median 12 months), all patients had an HIV-1 RNA < 400 copies/mL and six had an HIV-1 RNA < 50 copies/mL. No serious adverse effects were reported.

In a subsequent abstract, the authors updated their results with the Expanded Access program.[8] Twenty-three adolescents had been treated by December 2007. At follow-up (median 9 months), 86% had an HIV-1 RNA < 400 copies/mL and 68% had an HIV-1 RNA < 50 copies/mL. Median CD4 cell count increased from 194 cells/mm3 to 402 cells/mm3 at 6 months. Only one patient had discontinued raltegravir, due to persistent headaches.

Additional information comes from a case report published in the Journal of Antimicrobial Chemotherapy in 2009.[9] The authors describe the successful use of raltegravir in the treatment of a 9-year-old boy who experienced efavirenz-associated liver failure. He was started on raltegravir, lamivudine, and zidovudine 6 months after transplantation, resulting in an undetectable viral load within 2 weeks and a CD4 cell count of 500 cells/mm3.

A case report published last year provides preliminary information on the potential role of raltegravir in infants.[10] Brolund and colleagues describe a 3-month-old infant initially treated with zidovudine, lamivudine, and nevirapine who developed multidrug-resistance. The authors initiated treatment with raltegravir using a dose of 6 mg/kg twice daily, lopinavir/ritonavir, and lamivudine. At 16 weeks, the infant's HIV-1 RNA decreased from 2.5 log10copies/mL to 164 copies/mL, and his CD4% increased from 37 to 39%. No adverse effects were noted and the patient demonstrated catch-up growth, moving from <3rd percentile to >25th percentile.

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