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Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship | Journal Article / Research | MSF Science Portal
Journal Article
|Research

Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship

Bhatt NB, Baudin E, Meggi B, da Silva C, Barrail-Tran A, Furlan V, Grinsztejn B, Bonnet MMB, Taburet AM
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Abstract
OBJECTIVES
We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial.

METHODS
Participants were randomly selected to receive either nevirapine at 200 mg twice daily (n = 256) or efavirenz at 600 mg daily (n = 270), both combined with two nucleoside analogues. Blood samples were drawn 12 h after nevirapine or efavirenz administration, while on tuberculosis treatment and after tuberculosis treatment discontinuation. In 62 participants, samples taken 12 h after drug administration were drawn weekly for the first month of ART. Sixteen participants participated in an extensive pharmacokinetic study of nevirapine. Concentrations were compared with the therapeutic ranges of 3000-8000 ng/mL for nevirapine and 1000-4000 ng/mL for efavirenz.

RESULTS
Nevirapine concentrations at the end of the first week of treatment (on antituberculosis drugs) did not differ from concentrations off tuberculosis treatment, but declined thereafter. Concentrations at steady-state were 4111 ng/mL at week 12 versus 6095 ng/mL at week 48 (P < 0.0001). Nevirapine concentrations <3000 ng/mL were found to be a risk factor for virological failure. Efavirenz concentrations were higher on than off tuberculosis treatment (2700 versus 2450 ng/mL, P < 0.0001).

CONCLUSIONS
The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment initiation but did not prevent the risk of virological failure. Results support the WHO recommendation to use efavirenz at 600 mg daily in patients on rifampicin-based antituberculosis therapy.

Countries

Mozambique

Subject Area

tuberculosisHIV/AIDS

Languages

English
DOI
10.1093/jac/dku348
Published Date
18 Sep 2014
PubMed ID
25239466
Journal
Journal of Antimicrobial Chemotherapy
Volume | Issue | Pages
Volume 70, Issue 1, Pages 225-32
Issue Date
2014-09-18
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