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Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review
Author(s) -
Atwine Daniel,
Bonnet Maryline,
Taburet AnneMarie
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13600
Subject(s) - efavirenz , medicine , tuberculosis , pharmacokinetics , coinfection , rifampicin , adverse effect , dosing , pharmacology , nevirapine , virology , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , pathology
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.