Profile of etravirine in the treatment of HIV in pediatrics

Walter Dehority,¹ Rolando M Viani<sup>2

1</sup>Department of Pediatrics, Division of Infectious Diseases, The University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, NM, USA; ²Department of Pediatrics, Division of Infectious Diseases, Center for AIDS Research, University of California, San Diego School of Medicine, Rady Children's Hospital, San Diego, CA, USA

Abstract: Etravirine is a non-nucleoside reverse transcriptase inhibitor now licensed for treatment of human immunodeficiency virus (HIV)-1 infection in both children over 6 years of age and adults. Etravirine demonstrates a high genetic barrier to the development of resistance, as multiple mutations are typically required prior to the onset of reduced susceptibility to the drug. It retains in vitro and clinical activity against many HIV-1 isolates, demonstrating resistance to other non-nucleoside reverse transcriptase inhibitors, such as efavirenz and nevirapine. Given the ability of HIV to develop resistance rapidly across the non-nucleoside reverse transcriptase inhibitor class of antiretrovirals, etravirine has a welcome place in the management of HIV-infected patients, particularly treatment-experienced individuals harboring non-nucleoside reverse transcriptase inhibitor mutations. Etravirine has been shown to improve CD4 counts and viral load significantly in HIV-infected adults on combination antiretroviral therapy when compared with placebo in a large, randomized controlled trial. Data on the utility of etravirine in children are still somewhat limited, although a recent pediatric trial has demonstrated adequate pharmacokinetics, safety, and efficacy of etravirine in a small number of HIV-infected children and adolescents. In both children and adults, rash appears to be the most common adverse effect described. Despite its high genetic barrier to resistance, evidence of mutations conferring etravirine resistance has been documented in both adult and pediatric patients. Such mutations have been best described in treatment-experienced populations, including those who have never been exposed to the drug. This review describes the existing literature on the use of etravirine in the pediatric population, and highlights future and ongoing directions of investigation.

Keywords: etravirine, pediatric, human immunodeficiency virus, antiretrovirals, non-nucleoside reverse transcriptase inhibitor