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 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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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

Bibliographical note

Funding Information:
Financial support. The START study was funded by the National Institute of Allergy and Infectious Diseases (UM1-AI068641 and UM1-AI120197); National Institutes of Health Clinical Center; National Cancer Institute; National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France); National Health and Medical Research Council (Australia); National Research Foundation (Denmark); Bundes ministerium für Bildung und Forschung (Germany); European AIDS Treatment Network; Medical Research Council (United Kingdom); National Institute for Health Research; National Health Service (United Kingdom); and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmith-Kline/ViiV Healthcare, Janssen Scientific Affairs, and Merck.

Funding Information:
Potential conflicts of interest. A. A. P. has received grants from ViiV Healthcare, Janssen Cilag, and Pfizer outside the submitted work. A. A. P., B. G., and S. S. (or the institutions where they work) have received grants from NIH during the conduct of the study. E. M. has received grants from Merck and Janssen outside the submitted work. P. M. F. has received personal fees from Merck outside the submitted work. C. K. has received consultancy fees from MSD, Janssen, and ViiV, research grant from ViiV and Janssen, and travel grants from MSD, Gilead, and Janssen outside the submitted work. J. S. M. has received grants from Fundación Fundación para la Investigación a Beneficio de Inmunocomprometidos/Latin America Coordination of Academic Research during the conduct of the study and grants from Pfizer, Stendahl, Gilead, Abbvie, BMS, and GSK outside the submitted work. C. A. received a grant from the University of Minnesota during the conduct of the study. P. B. is an employee of the US Department of Health and Human Services, National Institutes of Mental Health. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords

  • HIV
  • efavirenz
  • suicidal behavior

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