Citation

Raffi F, Pozniak AL, Wainberg MA. Journal of Antimicrobial Chemotherapy 2014; 69(7): 1742-1747.

Copyright

(Copyright © 2014)

DOI

10.1093/jac/dku058

PMID

unavailable

Abstract

Efavirenz has been recommended as a preferred third agent together with two nucleos(t)ides for first-line combination antiretroviral therapy (ART) for >15 years. The availability of efavirenz in a fixed-dose combination makes it very attractive. However, because of (i) adverse events associated with efavirenz, (ii) a poorer overall efficacy of efavirenz compared with newer antiretrovirals, (iii) the ranking of efavirenz as FDA Pregnancy Category D and (iv) the relatively high prevalence of transmitted drug-resistance mutations, there is a need to reconsider the role of efavirenz in first-line ART. We review the available evidence that challenges efavirenz's current position in first-line HIV treatment guidelines. Apart from its animal teratogenic potential, and moderate neuropsychiatric adverse events associated with its use, efavirenz has recently been associated with an increased risk of suicidality when compared with other antiretroviral drugs. Most importantly, efavirenz has demonstrated overall inferior efficacy to various comparator drugs, which include rilpivirine, raltegravir and dolutegravir, in antiretroviral-naive patients. Furthermore, epidemiological data indicate that the prevalence of non-nucleoside reverse transcriptase inhibitor resistance has reached 5%-8% in various parts of the world, and minority transmitted non-nucleoside reverse transcriptase inhibitor resistance-associated mutations can have a negative impact on the outcome of first-line efavirenz-based ART. Based on considerations of efficacy, toxicity and resistance, it is time to reconsider the routine use of efavirenz in ART. This, of course, presupposes that other antiretrovirals will be available in place of efavirenz, and may not be applicable in certain developing country settings where this is not the case. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Language: en

Keywords

Humans; human; suicide; Suicide; drug use; suicidal behavior; risk assessment; article; mental disease; Human immunodeficiency virus infection; epidemiological data; practice guideline; efavirenz; HIV Infections; drug efficacy; neurologic disease; highly active antiretroviral therapy; Antiretroviral Therapy, Highly Active; randomized controlled trial (topic); raltegravir; Benzoxazines; antiviral therapy; antiviral resistance; Drug Resistance, Viral; meta analysis (topic); multicenter study (topic); rilpivirine; phase 3 clinical trial (topic); benzoxazine derivative; dolutegravir; Drug resistance; HIV clinical trials; HIV type 1; Neuropsychiatric adverse events; Non-nucleoside reverse transcriptase inhibitors