Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review.

ABSTRACT

AIMS: Efavirenz (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. METHODS: We 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. RESULTS: Of 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 4000 ng ml-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. CONCLUSIONS: Anti-TB drug coadministration minimally affect the EFV exposure, efficacy and safety among TB-HIV coinfected African and Asian patients. This supports the current 600 mg EFV dosing when coadministered with anti-TB drugs.