Comparative safety and neuropsychiatric adverse events associated with efavirenz use in first-line antiretroviral therapy: A systematic review and meta-analysis of randomized trials

Nathan Ford, Zara Shubber, Anton Pozniak, Marco Vitoria, Meg Doherty, Catherine Kirby, Alexandra Calmy

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Efavirenz (EFV) is widely used for the treatment of antiretroviral-naive HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric events. We systematically reviewed the safety of EFV in first-line therapy. Methods: Four databases were searched until October 2014 for randomized trials comparing EFV against non-EFV-based regimens for the treatment of antiretroviral-naive HIV-positive adults and children. The primary outcome was drug discontinuation as a result of any adverse event. Relative risks and proportions were pooled using random-effects meta-analysis. Results: Forty-two trials were included for review. A lower relative and absolute risk of discontinuations due to adverse drug reactions was seen with EFV compared to nevirapine. The relative and absolute risk of discontinuation was greater for EFV compared with low-dose EFV, rilpivirine, tenofovir, atazanavir, and maraviroc. The relative risk of discontinuation was greater for EFV compared with dolutegravir and raltegravir, but absolute risks were not significantly different. There was no difference in the risk of any severe clinical adverse events for any comparison. With the exception of dizziness, fewer than 10% of patients exposed to EFV experienced any other specific type of neuropsychiatric event. No suicides were reported. Conclusions: This review found that over 90% of patients remained on an EFV-based first-line regimen after an average follow-up time of 78 weeks. The relative risk of discontinuations due to adverse events was higher for EFV compared with most other first-line options, but absolute differences were less than 5% for all comparisons.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume69
Issue number4
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Central nervous system events
  • Efavirenz
  • Neuropsychiatric adverse events
  • Randomized trials
  • Suicide

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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