Association Between Efavirenz and Increased Risk for Suicidality

July 8, 2014

Association Between Efavirenz and Increased Risk for Suicidality

  1. Carlos del Rio, MD

Analysis of data from four studies showed a doubled risk for suicidality among participants initiating ART with an efavirenz-containing regimen compared with an efavirenz-free regimen.

  1. Carlos del Rio, MD

Efavirenz has long been a preferred component of initial antiretroviral therapy (ART) regimens for patients with HIV infection. Although the drug is effective and generally safe, it is associated with central nervous system side effects. To investigate the relation between efavirenz use and suicidality, researchers reviewed data from four AIDS Clinical Trials Group studies (A5095, A5142, A5175, A5202) in which some participants were randomized to initiate ART with an efavirenz-containing regimen.

The studies involved a total of 5332 participants (73% men; 32% with documented psychiatric history or recent prestudy psychoactive medication use; median age, 37), of whom 3241 were randomized to an efavirenz-containing regimen and 2091 to an efavirenz-free regimen. Median follow-up was 96 weeks.

Suicidality — suicidal ideation or attempted or completed suicide — was reported for 62 participants (47 in the efavirenz-containing arms vs. 15 in the efavirenz-free arms). Efavirenz-group participants had significantly higher rates of both attempted suicide (2.90 vs. 1.22/1000 person-years) and completed suicide (0.90 vs. 0.18/1000 person-years). On multivariable analysis, use of an efavirenz-containing regimen, history of injection-drug use, psychiatric history or recent prestudy use of psychoactive medications, and lower baseline weight were each significantly associated with increased risk for suicidality.


Among ART-naive participants in these clinical trials, the risk for suicidality was twice as high in the efavirenz-containing groups as in the efavirenz-free groups. Although suicidality was uncommon overall, the findings suggest that for patients with a history of injection-drug use or psychiatric comorbidity, choosing an alternative regimen for initial therapy — or close monitoring for the first few months after starting an efavirenz-containing regimen — may be advisable. In the U.S. and other countries where there are excellent efavirenz-free first-line regimens, suicide risk should be considered when deciding which regimen is best for the patient.

Editor Disclosures at Time of Publication

  • Disclosures for Carlos del Rio, MD at time of publication Grant / Research support NIH; NIH/National Institute of Allergy and Infectious Diseases; NIH/Fogarty International Center; CDC; NIH/National Institute on Drug Abuse; MANILA Consulting Group, Inc.; NIH/National Institute of Mental Health; Janssen Services; Addis Ababa University; George Washington University Editorial boards AIDS Research and Human Retroviruses; Journal of AIDS Leadership positions in professional societies HIV Medicine Association (Board of Directors); International AIDS Society-USA (Board of Directors)


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