Risk of suicidal behavior with use of efavirenz: Results from the strategic timing of antiretroviral treatment trial

Alejandro Arenas-Pinto, Birgit Grund, Shweta Sharma, Esteban Martinez, Nathan W Cummins, Julie Fox, Karin L. Klingman, Dalibor Sedlacek, Simon Collins, Patricia M. Flynn, William M. Chasanov, Eynat Kedem, Christine Katlama, Juan Sierra-Madero, Claudia Afonso, Pim Brouwers, David A. Cooper

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Abstract

Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalClinical Infectious Diseases
Volume67
Issue number3
DOIs
StatePublished - Jul 18 2018

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efavirenz
Risk-Taking
Mental Disorders
Group Psychotherapy
Therapeutics
Self-Injurious Behavior
CD4 Lymphocyte Count
Random Allocation
Proportional Hazards Models

Keywords

  • efavirenz
  • HIV
  • suicidal behavior

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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Risk of suicidal behavior with use of efavirenz : Results from the strategic timing of antiretroviral treatment trial. / Arenas-Pinto, Alejandro; Grund, Birgit; Sharma, Shweta; Martinez, Esteban; Cummins, Nathan W; Fox, Julie; Klingman, Karin L.; Sedlacek, Dalibor; Collins, Simon; Flynn, Patricia M.; Chasanov, William M.; Kedem, Eynat; Katlama, Christine; Sierra-Madero, Juan; Afonso, Claudia; Brouwers, Pim; Cooper, David A.

In: Clinical Infectious Diseases, Vol. 67, No. 3, 18.07.2018, p. 420-429.

Research output: Contribution to journalArticle

Arenas-Pinto, A, Grund, B, Sharma, S, Martinez, E, Cummins, NW, Fox, J, Klingman, KL, Sedlacek, D, Collins, S, Flynn, PM, Chasanov, WM, Kedem, E, Katlama, C, Sierra-Madero, J, Afonso, C, Brouwers, P & Cooper, DA 2018, 'Risk of suicidal behavior with use of efavirenz: Results from the strategic timing of antiretroviral treatment trial', Clinical Infectious Diseases, vol. 67, no. 3, pp. 420-429. https://doi.org/10.1093/cid/ciy051
Arenas-Pinto, Alejandro ; Grund, Birgit ; Sharma, Shweta ; Martinez, Esteban ; Cummins, Nathan W ; Fox, Julie ; Klingman, Karin L. ; Sedlacek, Dalibor ; Collins, Simon ; Flynn, Patricia M. ; Chasanov, William M. ; Kedem, Eynat ; Katlama, Christine ; Sierra-Madero, Juan ; Afonso, Claudia ; Brouwers, Pim ; Cooper, David A. / Risk of suicidal behavior with use of efavirenz : Results from the strategic timing of antiretroviral treatment trial. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 3. pp. 420-429.
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abstract = "Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8{\%}) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75{\%}), less often in those with psychiatric diagnoses (40{\%}) than without (77{\%}). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.",
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AU - Arenas-Pinto, Alejandro

AU - Grund, Birgit

AU - Sharma, Shweta

AU - Martinez, Esteban

AU - Cummins, Nathan W

AU - Fox, Julie

AU - Klingman, Karin L.

AU - Sedlacek, Dalibor

AU - Collins, Simon

AU - Flynn, Patricia M.

AU - Chasanov, William M.

AU - Kedem, Eynat

AU - Katlama, Christine

AU - Sierra-Madero, Juan

AU - Afonso, Claudia

AU - Brouwers, Pim

AU - Cooper, David A.

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N2 - Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.

AB - Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.

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