Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high HIV and tuberculosis burden countries: A systematic review

AIMS: Efavirenz (EFV) and Rifampicin-Isoniazid (RH) are cornerstone drugs in HIV-tuberculosis (TB) co-infection 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 co-administration in co-infected patients. Two reviewers conducted article screening and data collection. RESULTS: Of 119 records retrieved, 22 were included (2 conducted in children), reporting either EFV mid-dose or pre-dose concentrations. In 19 studies, median or mean concentrations on RH range between 1000-4000ng/mL, the so called therapeutic range. The proportion of patients with sub-therapeutic concentration on RH ranged between 3.1 to 72.2%, in 12 studies including 1 conducted in children. The proportion of patients with supra-therapeutic concentration ranged between 19.6 to 48.0% in 6 adult studies and 1 child study. Five of 8 studies reported virological suppression > 80%. The association between any grade hepatic and central nervous system adverse effects with EFV / RH interaction was demonstrated in 2 and 3 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-tuberculosis drug co-administration minimally affect the EFV exposure, efficacy and safety among TB-HIV co-infected African and Asian patients. This supports the current 600 mg EFV dosing when co administered with antituberculosis drugs

• Population(s)
  • General HIV+ population
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Tuberculosis