Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data

Ann Intern Med. 2014 Jul 1;161(1):1-10. doi: 10.7326/M14-0293.


Background: The relationship between efavirenz use and suicidality is not well-defined.

Objective: To compare time to suicidality with efavirenz-containing versus efavirenz-free antiretroviral regimens for initial treatment of HIV.

Design: Participant-level data were analyzed from 4 AIDS Clinical Trials Group, antiretroviral-naive studies conducted from 2001 to 2010. Within each study, participants were randomly assigned to an efavirenz-containing (n = 3241) or efavirenz-free (n = 2091) regimen. ( NCT00013520 [A5095], NCT00050895 [A5142], NCT00084136 [A5175], and NCT00118898 [A5202]).

Setting: AIDS Clinical Trials Group sites; 74% of participants enrolled in the United States.

Patients: Antiretroviral-naive participants.

Intervention: Efavirenz versus efavirenz-free regimens.

Measurements: Suicidality was defined as suicidal ideation or attempted or completed suicide. Groups were compared with a hazard ratio and 95% CI estimated from a Cox model, stratified by study.

Results: Seventy-three percent of participants were men, the median age was 37 years, and 32% had documented psychiatric history or received psychoactive medication within 30 days before entering the study. Median follow-up was 96 weeks. Suicidality incidence per 1000 person-years was 8.08 (47 events) in the efavirenz group and 3.66 (15 events) in the efavirenz-free group (hazard ratio, 2.28 [95% CI, 1.27 to 4.10]; P = 0.006). Incidence of attempted or completed suicide was 2.90 (17 events) and 1.22 (5 events) in the efavirenz and efavirenz-free groups, respectively (hazard ratio, 2.58 [CI, 0.94 to 7.06]; P = 0.065). Eight suicides in the efavirenz group and 1 in the efavirenz-free group were reported.

Limitation: There was not a standardized questionnaire about suicidal ideation or attempt. Efavirenz was open-label in 3 of 4 studies.

Conclusion: Initial treatment with an efavirenz-containing antiretroviral regimen was associated with a 2-fold increased hazard of suicidality compared with a regimen without efavirenz.

Primary funding source: National Institutes of Health.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alkynes
  • Anti-Retroviral Agents / adverse effects*
  • Benzoxazines / adverse effects*
  • Cause of Death
  • Cyclopropanes
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Humans
  • Male
  • RNA, Viral / analysis
  • Randomized Controlled Trials as Topic
  • Suicidal Ideation*
  • Suicide / statistics & numerical data*
  • Suicide, Attempted / statistics & numerical data
  • Viral Load


  • Alkynes
  • Anti-Retroviral Agents
  • Benzoxazines
  • Cyclopropanes
  • RNA, Viral
  • efavirenz

Associated data