title: Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis of Randomized Trials.
abstract: BACKGROUND
  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.
authors: *Department of HIV/AIDS, World Health Organization, Geneva, Switzerland; †Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom; ‡Chelsea and Westminster NHS Hospital Foundation Trust and St Stephens AIDS Trust, London, United Kingdom; §Lawson Unit, Royal Sussex County Hospital, Brighton, United Kingdom; and ‖HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Geneva, Switzerland.
authors: Nathan
authors: N
authors: Ford
authors: Zara
authors: Z
authors: Shubber
authors: Anton
authors: A
authors: Pozniak
authors: Marco
authors: M
authors: Vitoria
authors: Meg
authors: M
authors: Doherty
authors: Catherine
authors: C
authors: Kirby
authors: Alexandra
authors: A
authors: Calmy
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D048588:Benzoxazines / Q000009:adverse effects* / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D003521:Cyclopropanes; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz