Efavirenz, Tenofovir and Emtricitabine Combined with First-Line Tuberculosis Treatment in Tuberculosis–Hiv-Coinfected Tanzanian Patients: A Pharmacokinetic and Safety Study

Abstract

Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Long‐Term Effect of Rifampicin‐Based Anti‐TB Regimen Coadministration on the Pharmacokinetic Parameters of Efavirenz and 8‐Hydroxy‐Efavirenz in Ethiopian Patients

“…In a relatively similar study design in south Indian patient populations, Ramachandran et al reported that even though C max and AUC 0–24 seemed to slightly but insignificantly decrease with RIF‐based cotreatment, they concluded that RIF coadministration did not significantly alter the PK parameters of EFV . Semvua et al reported a similar outcome in Tanzanian patients, although C max , C min , and AUC 0–24 were slightly but insignificantly lower during RIF cotreatment . No effects of RIF coadministration on plasma concentrations of EFV at C mid‐dose or C min were reported in Cambodian, South African, Thai, Ugandan, and Tanzanian patients .…”

“…These methods are more variable and less reliable than methods that determine PK parameters from multiple concentration values in a subject. Of studies that investigated the impact of RIF‐based anti‐TB treatment on PK parameters, a few involved healthy volunteers or pediatric patients or did not consider pharmacogenetic information . A study by Bertrand et al used sparse PK samples from 10 subjects collected 6 months after stopping RIF‐based anti‐TB treatment.…”

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

“…Of the 14 studies conducted among adult patients that reported EFV concentrations on and off RH, 10 were in Africa and four in Asia. Notably, among the 10 adult studies conducted in Africa, six reported higher EFV concentration during RH coadministration compared to the off‐RH period, although the difference is highly variable, ranging from 3.7% to 33.3% across studies and countries . The remaining four adult African studies reported a lower EFV concentration while on RH, still with a difference that is highly variable, ranging from –16.3 to –33.3% .…”

“…In adults, EFV was systematically administered at a dose of 600 mg day –1 of which one study also had EFV 800 mg day –1 dose administered to a selected comparative group of patients . EFV was administered at bed‐time to improve the tolerability and reduce adverse events , except for four adult studies where it was taken in the morning and a 6‐month anti‐TB treatment was used and administered daily at recommended dosing in all studies except one with intermittent administration . Thirteen studies (59%) reported EFV concentrations on and off RH within the same patients.…”

“…Studies conducted among adult patients in Tanzania and Thailand or in children in South Africa highlight within country variability with regard to effect of RH on EFV concentrations , which could partially be explained by the small sample size, or differences in methodology used and the pharmacogenetics within different ethnic groups. As highlighted in the review by Colic et al .…”