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

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 efavirenz in first-line therapy. METHODS: 4 databases were searched up to October 2014 for randomized trials comparing efavirenz against non-efavirenz 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: 42 trials were included for review. A lower relative and absolute risk of discontinuations due to adverse drug reactions was seen with efavirenz compared to nevirapine. The relative and absolute risk of discontinuation was greater for efavirenz compared to low dose efavirenz, rilpivirine, tenofovir, atazanavir, and maraviroc. The relative risk of discontinuation was greater for efavirenz compared to 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 efavirenz experienced any other specific type of neuropsychniatric event. No suicides were reported. DISCUSSION: 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 efavirenz compared to most other first-line options but absolute differences were less than 5% for all comparisons.

• Population(s)
  • General HIV+ population
• Engagement and Care Cascade
  • Treatment
• Mental Health
  • Psychiatric disorders
• Health Systems
  • Delivery arrangements