Safety of long-term isoniazid preventive therapy in children with HIV: a comparison of two dosing schedules.

SETTING

Two paediatric hospitals in Cape Town, South Africa.

OBJECTIVE

To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus (HIV) infected children receiving long-term isoniazid preventive therapy (IPT).

DESIGN

Randomised trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks; placebo was discontinued early. Alanine transaminase (ALT) was measured at baseline, 6-monthly and during illness: an increase of ≥10 times the upper limit of normal defined severe liver injury.

RESULTS

Of 324 children enrolled, 297 (91.6%) received IPT (559.1 person-years [py]). Baseline median age was 23 months (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A total of 207 (63.9%) children received combination antiretroviral therapy: 19 developed severe liver injury, 16 while receiving IPT. Among these there were 8 cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure; one died of an unrelated cause. All surviving children subsequently tolerated IPT.

CONCLUSIONS

This study suggests that long-term IPT has a low toxicity risk in HIV-infected children. In the absence of chronic viral hepatitis, IPT can be safely re-introduced following recovery from liver injury.