Clinical utility of raltegravir for the treatment of HIV infection in children and adolescents

James Nuttall,¹ Tammy Meyers,² Brian Eley<sup>1

1</sup>Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ²Department of Paediatrics, Chris Hani Baragwanath Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Abstract: Raltegravir (RAL) is the first integrase strand transfer inhibitor and has been shown to provide potent antiretroviral (ARV) activity against human immunodeficiency virus type 1 (HIV-1) in both ARV treatment-naïve and treatment-experienced individuals. Following initial US Food and Drug Administration (FDA) approval of RAL for treatment of HIV-1-infected adults in 2007, an ongoing pharmacokinetic, safety, and efficacy study in ARV-experienced children and adolescents led to extension of FDA approval to children and adolescents aged 2–18 years in 2011. Availability of chewable tablets for children aged 2–11 years is a significant advantage, and twice-daily dosing is recommended based on pharmacokinetic parameters. Granules for oral suspension in children 4 weeks to 2 years of age are currently under evaluation and clinical trials in neonates are imminent. Coadministration of RAL and the anti-tuberculosis drug rifampin (RIF) results in reduced RAL exposure. Evaluation of a double RAL dosing strategy in children requiring cotreatment with RIF is planned. RAL is generally well tolerated and has a good overall safety profile. Further data is required for children before RAL can be recommended in first-line ARV treatment regimens. RAL is also under investigation for use in preventing mother-to-child transmission both during pregnancy and in the HIV-exposed neonate. Currently, the main therapeutic role for RAL in children is for treatment failure and multi-drug resistant cases where the inclusion of RAL in combination with optimal background therapy has demonstrated successful outcomes. Increased availability of RAL and the introduction of second-generation integrase inhibitors are likely to further extend the utility of this class of ARV drugs.


Keywords: antiretroviral therapy, integrase strand transfer inhibitor, raltegravir, HIV-1