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

Abstract

James Nuttall,1 Tammy Meyers,2 Brian Eley11Paediatric 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 AfricaAbstract: 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