Atwine D., Bonnet Maryline, Taburet A. M. (2018). Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries : a systematic review. British Journal of Clinical Pharmacology, 84 (8), p. 1641-1658. ISSN 0306-5251.
Titre du document
Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries : a systematic review
British Journal of Clinical Pharmacology, 2018,
84 (8), p. 1641-1658 ISSN 0306-5251
AimsEfavirenz (EFV) and rifampicin-isoniazid (RH) are cornerstone drugs in human immunodeficiency virus (HIV)-tuberculosis (TB) coinfection treatment but with complex drug interactions, efficacy and safety challenges. We reviewed recent data on EFV and RH interaction in TB/HIV high-burden countries. MethodsWe conducted a systematic review of studies conducted in the high TB/HIV-burden countries between 1990 and 2016 on EFV pharmacokinetics during RH coadministration in coinfected patients. Two reviewers conducted article screening and data collection. ResultsOf 119 records retrieved, 22 were included (two conducted in children), reporting either EFV mid-dose or pre-dose concentrations. In 19 studies, median or mean concentrations of RH range between 1000 and 4000ngml(-1), the so-called therapeutic range. The proportion of patients with subtherapeutic concentration of RH ranged between 3.1 and 72.2%, in 12 studies including one conducted in children. The proportion of patients with supratherapeutic concentration ranged from 19.6 to 48.0% in six adult studies and one child study. Five of eight studies reported virological suppression >80%. The association between any grade hepatic and central nervous system adverse effects with EFV/RH interaction was demonstrated in two and three studies, respectively. The frequency of the CYP2B6 516G>T polymorphism ranged from 10 to 28% and was associated with higher plasma EFV concentrations, irrespective of ethnicity. ConclusionsAnti-TB drug coadministration minimally affect the EFV exposure, efficacy and safety among TB-HIV coinfected African and Asian patients. This supports the current 600mg EFV dosing when coadministered with anti-TB drugs.
