title: No Evidence of an Association Between Efavirenz Exposure and Suicidality Among HIV Patients Initiating Antiretroviral Therapy in a Retrospective Cohort Study of Real World Data.
abstract: Recently, published studies have reported conflicting results regarding the association between efavirenz exposure and the risk of suicidality among patients with human immunodeficiency virus. The objective of this analysis was to compare the rate of suicidality among patients initiating efavirenz-containing versus efavirenz-free antiretroviral (ARV) regimens.This retrospective cohort study used US administrative claims data for commercially and Medicaid-insured individuals for the years 2006 to 2013. ARV-naive patients aged ≥12 years initiating an efavirenz-containing or efavirenz-free ARV regimen with ≥6 months of continuous insurance enrollment prior to ARV initiation were selected. The primary outcome was suicidality, defined as the occurrence of any medical claim with a diagnosis code for suicidal ideation or an inpatient or emergency department medical claim for suicide attempt. Unadjusted incidence rates were calculated and propensity score-adjusted hazard ratios were estimated to account for differences in patient characteristics.There were 19,983 patients (efavirenz-containing, n = 11,187; efavirenz-free, n = 8796) in the commercial database and 5154 patients (efavirenz-containing, n = 2224; efavirenz-free, n = 2930) in the Medicaid database. Unadjusted incidence rates (95% confidence interval [CI]) of suicidality per 1000 person-years were: commercial, efavirenz-containing (3.3 [2.4-4.4]), efavirenz-free (4.0 [2.7-5.8]); Medicaid, efavirenz-containing (25.7 [18.8-34.4]), efavirenz-free (40.6 [31.9-50.9]). In propensity score-adjusted analyses, efavirenz use was not associated with suicidality: adjusted hazard ratio (95% CI) of suicidality compared with efavirenz-free regimen, commercial, 1.029 (0.636-1.665); Medicaid, 0.902 (0.617-1.319).This analysis found no conclusive evidence of an increased risk of suicidality among patients initiating an efavirenz-containing ARV regimen. However, channeling bias may exist even after adjusting for measured patient characteristics.
authors.affiliation: From the Bristol-Myers Squibb, Global Pharmacovigilance and Epidemiology, Wallingford, Connecticut (ETN); Bristol-Myers Squibb, Global Pharmacovigilance and Epidemiology, Hopewell, New Jersey (JC, DS); Truven Health Analytics, Bethesda, Maryland (AMF, SSJ, BCC); Bristol-Myers Squibb, Health Economics and Outcomes Research (LCR); and Bristol-Myers Squibb, US Medical, Plainsboro, New Jersey (AV-K).
authors.forename: Ella T
authors.initials: ET
authors.lastname: Nkhoma
authors.forename: John
authors.initials: J
authors.lastname: Coumbis
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Farr
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Johnston
authors.forename: Bong Chul
authors.initials: BC
authors.lastname: Chu
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Rosenblatt
authors.forename: Daniel
authors.initials: D
authors.lastname: Seekins
authors.forename: Angelina
authors.initials: A
authors.lastname: Villasis-Keever
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000523:psychology; D048588:Benzoxazines / Q000009:adverse effects* / Q000627:therapeutic use; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D059020:Suicidal Ideation; D013406:Suicide, Attempted / Q000706:statistics & numerical data
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
references.citation: J Behav Med. 2005 Apr;28(2):149-56
references.pmid: 15957570
references.citation: Pharmacoepidemiol Drug Saf. 2010 Dec;19(12):1263-75
references.pmid: 20922709
references.citation: J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19512
references.pmid: 25394021
references.citation: AIDS Rev. 2010 Apr-Jun;12(2):67-75
references.pmid: 20571601
references.citation: Ann Behav Med. 2002 Spring;24(2):141-8
references.pmid: 12054319
references.citation: AIDS Rev. 2009 Apr-Jun;11(2):103-9
references.pmid: 19529750
references.citation: Expert Opin Drug Saf. 2007 Mar;6(2):147-54
references.pmid: 17367260
references.citation: CMAJ Open. 2015 Apr 02;3(2):E140-8
references.pmid: 26389091
references.citation: AIDS Behav. 2011 Nov;15(8):1803-18
references.pmid: 21484283
references.citation: Psychol Health Med. 2011 Oct;16(5):588-611
references.pmid: 21745024
references.citation: Am J Epidemiol. 2006 Jun 15;163(12):1149-56
references.pmid: 16624967
references.citation: Soc Psychiatry Psychiatr Epidemiol. 2000 Jul;35(7):288-96
references.pmid: 11016523
references.citation: HIV Med. 2003 Jan;4(1):62-6
references.pmid: 12534961
references.citation: J Affect Disord. 2012 Feb;136(3):993-9
references.pmid: 21784531
references.citation: Clin Infect Dis. 2005 Dec 1;41(11):1648-53
references.pmid: 16267739
references.citation: Pharmacoepidemiol Drug Saf. 2013 Jul;22(7):769-75
references.pmid: 23412882
references.citation: J Int AIDS Soc. 2014 Sep 04;17:19214
references.pmid: 25192857
references.citation: Ann Intern Med. 2014 Jul 1;161(1):1-10
references.pmid: 24979445