Tolerability of Isoniazid Preventive Therapy in an HIV-Infected Cohort of Paediatric and Adolescent Patients on Antiretroviral Therapy from a Resource-Limited Setting: A Retrospective Cohort Study

Abstract

BackgroundTreating patients with latent tuberculosis infection (LTBI) to prevent development of active disease is an essential strategy for eliminating TB. There are concerns regarding the use of isoniazid due to the potential for hepatotoxicity. This study was conducted to determine the incidence of adverse hepatic events after isoniazid preventive therapy (IPT) commencement in a cohort of HIV-infected paediatric and adolescent patients on antiretroviral therapy (ART).MethodsThis was a retrospective records review, using data from HIV-infected paediatric and adolescent patients collected during routine clinical visits at Newlands Clinic, Harare, Zimbabwe. Patients included in the analysis had commenced IPT between January 2014 and June 2015 (inclusive) whilst receiving ART. A survival analysis was conducted for the period that participants were receiving IPT with end-points defined by grade 3 or grade 4 elevations in alanine aminotransferase (ALT) levels.ResultsData from 438 patients commenced on IPT were analysed; 202 (46.1%) of them were female. The median age at IPT commencement was 10 (IQR = 7–12) years. Twenty-eight patients developed grade 3 or 4 elevations in ALT. Concomitant use of nevirapine as part of an ART regimen was the only factor that showed a statistically significant association with ALT elevation [relative risk (RR): 2.7; confidence interval (CI): 1.2–6.3, p = 0.012] compared with those not receiving nevirapine. The incidence of grade 3 or 4 elevations in ALT was 31.5/100 person-years (CI 20.9–45.5).ConclusionThe incidence of IPT-associated ALT elevations was high in this population. We recommend vigilant monitoring of liver enzymes for patients receiving IPT, especially in patients concomitantly receiving nevirapine.