Discontinuation of Efavirenz in Paediatric Patients: Why do Children Switch?

Abstract

Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) is used globally as first-line antiretroviral therapy (ART) in combination with a dual nucleoside backbone in adults and children from 3years of age. Up to 40% of adults taking efavirenz report central nervous system (CNS) adverse effects, and the rates of discontinuation of efavirenz-based treatment are higher than other first-line regimens. Data on efavirenz discontinuation are more limited for children and adolescents. In this study, we aimed to describe our single-centre paediatric experience of efavirenz. Retrospective case-note audit of children and adolescents with perinatally acquired HIV who ever received efavirenz. From 1998 and 2014, 51 children and adolescents aged ≤18years received efavirenz-based treatment. Median age at efavirenz initiation was 9.4years (interquartile range [IQR] 7-13). More than half (30/51; 59%) subsequently switched off efavirenz-15 (29%) following virological failure with NNRTI-associated resistance mutations, and 16 (30%) after reporting adverse effects. Of those who experienced adverse effects, one-fifth (19.6%) described CNS adverse effects, including sleep disturbance, reduced concentration, headaches, mood change and psychosis. Four children (three males) developed gynaecomastia, two developed hypercholesterolaemia, and one child developed Stevens-Johnson syndrome. Comparison between those reporting side effects and the rest of the cohort showed no difference in age, sex, initial CD4 cell count, viral suppression, length of efavirenz-based treatment, weight, or efavirenz dose per kilogram. Median time to switch was 25 months (IQR 10-71) in those who experienced side effects and 22 months (IQR 12-50) for virological failure. One individual experienced both virological failure and adverse effects. Almost two-thirds of this paediatric cohort switched from efavirenz-based treatment to an alternative regimen, due in equal proportions to both virological failure and toxicity. The majority of side effects involved the CNS. First-line regimens with improved tolerability and a higher genetic barrier to resistance should be the preferred option for children.