title: 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.
abstract: 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.
  
  
  METHODS
  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. (ClinicalTrials.gov: NCT00013520 [A5095], NCT00050895 [A5142], NCT00084136 [A5175], and NCT00118898 [A5202]).
  
  
  METHODS
  AIDS Clinical Trials Group sites; 74% of participants enrolled in the United States.
  
  
  METHODS
  Antiretroviral-naive participants.
  
  
  METHODS
  Efavirenz versus efavirenz-free regimens.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  There was not a standardized questionnaire about suicidal ideation or attempt. Efavirenz was open-label in 3 of 4 studies.
  
  
  CONCLUSIONS
  Initial treatment with an efavirenz-containing antiretroviral regimen was associated with a 2-fold increased hazard of suicidality compared with a regimen without efavirenz.
  
  
  BACKGROUND
  National Institutes of Health.
authors: Katie R
authors: KR
authors: Mollan
authors: Marlene
authors: M
authors: Smurzynski
authors: Joseph J
authors: JJ
authors: Eron
authors: Eric S
authors: ES
authors: Daar
authors: Thomas B
authors: TB
authors: Campbell
authors: Paul E
authors: PE
authors: Sax
authors: Roy M
authors: RM
authors: Gulick
authors: Lumine
authors: L
authors: Na
authors: Lauren
authors: L
authors: O'Keefe
authors: Kevin R
authors: KR
authors: Robertson
authors: Camlin
authors: C
authors: Tierney
mesh_terms: D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D048588:Benzoxazines / Q000009:adverse effects*; D002423:Cause of Death; D003521:Cyclopropanes; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D059020:Suicidal Ideation; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000706:statistics & numerical data; D019562:Viral Load
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; C098320:efavirenz