Association of History of Injection Drug Use with External Cause-Related Mortality Among Persons Linked to HIV Care in an Urban Clinic, 2001–2015

  • Kanal Singh
  • Geetanjali Chander
  • Bryan Lau
  • Jessie K. Edwards
  • Richard D. Moore
  • Catherine R. LeskoEmail author
Original Paper


High mortality rates among persons with HIV with a history of injection drug use (PWID) are thought to be driven in part by higher rates of external cause-related mortality. We followed 4796 persons aged 18–70 engaged in continuity HIV care from 2001 to 2015 until death or administrative censoring. We compared cause-specific (csHR) and subdistribution hazards (sdHR) of death due to external causes among PWID and persons who acquired their HIV infection through other routes (non-IDU). We standardized estimates on age, sex, race, and HIV-related health status. The standardized csHR for external cause-related death was 3.57 (95% CI 2.39, 5.33), and the sdHR was 3.14 (95% CI 2.16, 4.55). The majority of external cause-related deaths were overdose-related and standardized sdHR was 4.02 (95% CI 2.40, 6.72). Absolute rate of suicide was low but the csHR for PWID compared to non-IDU was most elevated for suicide (6.50, 95% CI 1.51, 28.03). HIV-infected PWID are at a disproportionately increased risk of death due to external causes, particularly overdose and suicide.


Cause-specific mortality Competing risks Injection drug use Injury-related mortality Survival 



This work was supported by NIH grants U01 DA036935 and P30 AI094189. The funders have had no influence on the design of this analysis or reporting of results.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10461_2019_2497_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)


  1. 1.
    Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d’Arminio Monforte A, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362(9377):22–9.CrossRefGoogle Scholar
  2. 2.
    Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43(1):27–34.CrossRefGoogle Scholar
  3. 3.
    Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, HIV Outpatient Study Investigators, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338(13):853–60.CrossRefGoogle Scholar
  4. 4.
    Lesko CR, Edwards JK, Moore RD, Lau B. A longitudinal, HIV care continuum: 10-year restricted mean time in each care continuum stage after enrollment in care, by history of injection drug use. AIDS. 2016;30(14):2227–34.CrossRefGoogle Scholar
  5. 5.
    Buchanan AL, Hudgens MG, Cole SR, Lau B, Adimora AA, Women’s Interagency HIVS. Worth the weight: using inverse probability weighted Cox models in AIDS research. AIDS Res Hum Retrovir. 2014;30(12):1170–7.CrossRefGoogle Scholar
  6. 6.
    Clarke JG, Stein MD, McGarry KA, Gogineni A. Interest in smoking cessation among injection drug users. Am J Addict. 2001;10(2):159–66.CrossRefGoogle Scholar
  7. 7.
    Artenie AA, Bruneau J, Roy E, Zang G, Lesperance F, Renaud J, et al. Licit and illicit substance use among people who inject drugs and the association with subsequent suicidal attempt. Addiction. 2015;110(10):1636–43.CrossRefGoogle Scholar
  8. 8.
    Howe CJ, Cole SR, Ostrow DG, Mehta SH, Kirk GD. A prospective study of alcohol consumption and HIV acquisition among injection drug users. AIDS. 2011;25(2):221–8.CrossRefGoogle Scholar
  9. 9.
    Chander G, Lau B, Moore RD. Hazardous alcohol use: a risk factor for non-adherence and lack of suppression in HIV infection. J Acquir Immune Defic Syndr. 2006;43(4):411–7.CrossRefGoogle Scholar
  10. 10.
    Lesko CR, Moore RD, Tong W, Lau B. Association of injection drug use with incidence of HIV-associated non-AIDS-related morbidity by age, 1995–2014. AIDS. 2016;30(9):1447–55.CrossRefGoogle Scholar
  11. 11.
    Nazrul Islam SK, Jahangir Hossain K, Ahmed A, Ahsan M. Nutritional status of drug addicts undergoing detoxification: prevalence of malnutrition and influence of illicit drugs and lifestyle. Br J Nutr. 2002;88(5):507–13.CrossRefGoogle Scholar
  12. 12.
    Amon JJ, Garfein RS, Ahdieh-Grant L, Armstrong GL, Ouellet LJ, Latka MH, et al. Prevalence of hepatitis C virus infection among injection drug users in the United States, 1994–2004. Clin Infect Dis. 2008;46(12):1852–8.CrossRefGoogle Scholar
  13. 13.
    Nambiar D, Weir A, Aspinall EJ, Stoové M, Hutchinson S, Dietze P, et al. Mortality and cause of death in a cohort of people who had ever injected drugs in Glasgow: 1982–2012. Drug Alcohol Depend. 2015;147:215–21.CrossRefGoogle Scholar
  14. 14.
    Mathers BM, Degenhardt L, Bucello C, Lemon J, Wiessing L, Hickman M. Mortality among people who inject drugs: a systematic review and meta-analysis. Bull World Health Organ. 2013;91(2):102–23.CrossRefGoogle Scholar
  15. 15.
    Bing EG, Burnam MA, Longshore D, Fleishman JA, Sherbourne CD, London AS, et al. Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry. 2001;58(8):721–8.CrossRefGoogle Scholar
  16. 16.
    Tucker JS, Burnam MA, Sherbourne CD, Kung FY, Gifford AL. Substance use and mental health correlates of nonadherence to antiretroviral medications in a sample of patients with human immunodeficiency virus infection. Am J Med. 2003;114(7):573–80.CrossRefGoogle Scholar
  17. 17.
    Braitstein P, Li K, Tyndall M, Spittal P, O’Shaughnessy MV, Schilder A, et al. Sexual violence among a cohort of injection drug users. Soc Sci Med. 2003;57(3):561–9.CrossRefGoogle Scholar
  18. 18.
    Marshall BDL, Fairbairn N, Li K, Wood E, Kerr T. Physical violence among a prospective cohort of injection drug users: a gender-focused approach. Drug Alcohol Depend. 2008;97(3):237–46.CrossRefGoogle Scholar
  19. 19.
    Moore RD. Understanding the clinical and economic outcomes of HIV therapy: the Johns Hopkins HIV clinical practice cohort. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(Suppl 1):S38–41.CrossRefGoogle Scholar
  20. 20.
    Services USDoHaH. ICD-10 cause-of-death lists for tabulating mortality statistics. Hyatsville: Centers for Disease Control and Prevention NCfHS; 2009.Google Scholar
  21. 21.
    Lu K, Tsiatis AA. Multiple imputation methods for estimating regression coefficients in the competing risks model with missing cause of failure. Biometrics. 2001;57(4):1191–7.CrossRefGoogle Scholar
  22. 22.
    Lau B, Lesko CR. Missingness in the setting of competing risks: from missing values to missing potential outcomes. Curr Epidemiol Rep. 2018. Scholar
  23. 23.
    Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the united states, 1970-2002. JAMA. 2005;294(10):1255–9.CrossRefGoogle Scholar
  24. 24.
    Cox DR. Regression models and life-tables. J Roy Stat Soc: Ser B (Methodol). 1972;34(2):187–220.Google Scholar
  25. 25.
    Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509.CrossRefGoogle Scholar
  26. 26.
    Aalen OO, Johansen S. Empirical transition matrix for nonhomogeneous markov-chains based on censored observations. Scand J Stat. 1978;5(3):141–50.Google Scholar
  27. 27.
    Cole SR, Hudgens MG, Brookhart MA, Westreich D. Risk. Am J Epidemiol. 2015;181(4):246–50.CrossRefGoogle Scholar
  28. 28.
    Cole SR, Hernan MA. Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed. 2004;75(1):45–9.CrossRefGoogle Scholar
  29. 29.
    Cole SR, Hernan MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol. 2008;168(6):656–64.CrossRefGoogle Scholar
  30. 30.
    Howe CJ, Cole SR, Westreich DJ, Greenland S, Napravnik S, Eron JJ Jr. Splines for trend analysis and continuous confounder control. Epidemiology. 2011;22(6):874–5.CrossRefGoogle Scholar
  31. 31.
    Bartlett JW, Taylor JM. Missing covariates in competing risks analysis. Biostatistics. 2016;17(4):751–63.CrossRefGoogle Scholar
  32. 32.
    White IR, Royston P. Imputing missing covariate values for the Cox model. Stat Med. 2009;28(15):1982–98.CrossRefGoogle Scholar
  33. 33.
    Raghunathan TE, Solenberger PW, Van Hoewyk J. IVEware: imputation and variance estimation software. Ann Arbor: Survey Methodology Program, Survey Research Center, Institute for Social Research, University of Michigan; 2002.Google Scholar
  34. 34.
    Rubin DB. Multiple imputation after 18+ years. J Am Stat Assoc. 1996;91(434):473–89.CrossRefGoogle Scholar
  35. 35.
    Bakoyannis G, Yiannoutsos CT. Impact of and correction for outcome misclassification in cumulative incidence estimation. PLoS ONE. 2015;10(9):e0137454.CrossRefGoogle Scholar
  36. 36.
    Moyer LA, Boyle CA, Pollock DA. Validity of death certificates for injury-related causes of death. Am J Epidemiol. 1989;130(5):1024–32.CrossRefGoogle Scholar
  37. 37.
    Davis JM, Suleta K, Corsi KF, Booth RE. A hazard analysis of risk factors of mortality in individuals who inject drugs in Denver, CO. AIDS Behav. 2017;21(4):1044–53.CrossRefGoogle Scholar
  38. 38.
    Joe GW, Lehman W, Simpson DD. Addict death rates during a four-year posttreatment follow-up. Am J Public Health. 1982;72(7):703–9.CrossRefGoogle Scholar
  39. 39.
    Joe GW, Simpson DD. Mortality rates among opioid addicts in a longitudinal study. Am J Public Health. 1987;77(3):347–8.CrossRefGoogle Scholar
  40. 40.
    Fugelstad A, Annell A, Rajs J, Agren G. Mortality and causes and manner of death among drug addicts in Stockholm during the period 1981–1992. Acta Psychiatr Scand. 1997;96(3):169–75.CrossRefGoogle Scholar
  41. 41.
    Frischer M, Goldberg D, Rahman M, Berney L. Mortality and survival among a cohort of drug injectors in Glasgow, 1982–1994. Addiction. 1997;92(4):419–27.CrossRefGoogle Scholar
  42. 42.
    Hall HI, McDavid K, Ling Q, Sloggett A. Determinants of progression to AIDS or death after HIV diagnosis, United States, 1996 to 2001. Ann Epidemiol. 2006;16(11):824–33.CrossRefGoogle Scholar
  43. 43.
    Davoli M, Perucci CA, Forastiere F, Doyle P, Rapiti E, Zaccarelli M, et al. Risk factors for overdose mortality: a case–control study within a cohort of intravenous drug users. Int J Epidemiol. 1993;22(2):273–7.CrossRefGoogle Scholar
  44. 44.
    Gilbert L, Primbetova S, Nikitin D, Hunt T, Terlikbayeva A, Momenghalibaf A, et al. Redressing the epidemics of opioid overdose and HIV among people who inject drugs in Central Asia: the need for a syndemic approach. Drug Alcohol Depend. 2013;132(1):S56–60.CrossRefGoogle Scholar
  45. 45.
    Nambiar D, Agius PA, Stoové M, Hickman M, Dietze P. Mortality in the Melbourne injecting drug user cohort study (MIX). Harm Reduct J. 2015;12:55.CrossRefGoogle Scholar
  46. 46.
    Fairbairn NS, Walley AY, Cheng DM, Quinn E, Bridden C, Chaisson C, et al. Mortality in HIV-infected alcohol and drug users in St. Petersburg, Russia. PLoS ONE. 2016;11(11):e0166539.CrossRefGoogle Scholar
  47. 47.
    Young TW, Pollock DA. Misclassification of deaths caused by cocaine: an assessment by survey. The Am J Forensic Med Pathol. 1993;14(1):43–7.CrossRefGoogle Scholar
  48. 48.
    Johns LE, Madsen AM, Maduro G, Zimmerman R, Konty K, Begier E. A case study of the impact of inaccurate cause-of-death reporting on health disparity tracking: New York City premature cardiovascular mortality. Am J Public Health. 2013;103(4):733–9.CrossRefGoogle Scholar
  49. 49.
    Filippatos G, Andriopoulos P, Panoutsopoulos G, Zyga S, Souliotis K, Gennimata V, et al. The quality of death certification practice in Greece. Hippokratia. 2016;20(1):19–25.Google Scholar
  50. 50.
    Haque AS, Shamim K, Siddiqui NH, Irfan M, Khan JA. Death certificate completion skills of hospital physicians in a developing country. BMC Health Serv Res. 2013;13:205.CrossRefGoogle Scholar
  51. 51.
    Alperovitch A, Bertrand M, Jougla E, Vidal JS, Ducimetiere P, Helmer C, et al. Do we really know the cause of death of the very old? Comparison between official mortality statistics and cohort study classification. Eur J Epidemiol. 2009;24(11):669–75.CrossRefGoogle Scholar
  52. 52.
    Rao C, Yang G, Hu J, Ma J, Xia W, Lopez AD. Validation of cause-of-death statistics in urban China. Int J Epidemiol. 2007;36(3):642–51.CrossRefGoogle Scholar
  53. 53.
    Swendsen J, Conway KP, Degenhardt L, Glantz M, Jin R, Merikangas KR, et al. Mental disorders as risk factors for substance use, abuse and dependence: results from the 10-year follow-up of the National Comorbidity Survey. Addiction. 2010;105(6):1117–28.CrossRefGoogle Scholar
  54. 54.
    Redonnet B, Chollet A, Fombonne E, Bowes L, Melchior M. Tobacco, alcohol, cannabis and other illegal drug use among young adults: the socioeconomic context. Drug Alcohol Depend. 2012;121(3):231–9.CrossRefGoogle Scholar
  55. 55.
    Ompad DC, Nandi V, Cerda M, Crawford N, Galea S, Vlahov D. Beyond income: material resources among drug users in economically-disadvantaged New York City neighborhoods. Drug Alcohol Depend. 2012;120(1–3):127–34.CrossRefGoogle Scholar
  56. 56.
    Campsmith ML, Rhodes PH, Hall HI, Green TA. Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006. J Acquir Immune Defic Syndr. 2010;53(5):619–24.Google Scholar
  57. 57.
    Suarez-Garcia I, Sobrino-Vegas P, Dalmau D, Rubio R, Iribarren JA, Blanco JR, et al. Clinical outcomes of patients infected with HIV through use of injected drugs compared to patients infected through sexual transmission: late presentation, delayed anti-retroviral treatment and higher mortality. Addiction. 2016;111(7):1235–45.CrossRefGoogle Scholar
  58. 58.
    Strathdee SA, Shoptaw S, Dyer TP, Quan VM, Aramrattana A. Towards combination HIV prevention for injection drug users: addressing addictophobia, apathy and inattention. Curr Opin HIV AIDS. 2012;7(4):320–5.CrossRefGoogle Scholar
  59. 59.
    Wheeler E, Jones TS, Gilbert MK, Davidson PJ. Opioid overdose prevention programs providing naloxone to laypersons—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(23):631–5.Google Scholar
  60. 60.
    Doe-Simkins M, Quinn E, Xuan Z, Sorensen-Alawad A, Hackman H, Ozonoff A, et al. Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs: a retrospective cohort study. BMC Public Health. 2014;14:297.CrossRefGoogle Scholar
  61. 61.
    Krug EG, Mercy JA, Dahlberg LL, Zwi AB. The world report on violence and health. Lancet. 2002;360(9339):1083–8.CrossRefGoogle Scholar
  62. 62.
    On murderous streets: crime and despair in Baltimore. In: The economist. New York: The Economist Ltd.; 2017.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kanal Singh
    • 1
  • Geetanjali Chander
    • 2
  • Bryan Lau
    • 1
  • Jessie K. Edwards
    • 3
  • Richard D. Moore
    • 1
    • 2
  • Catherine R. Lesko
    • 1
    Email author
  1. 1.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Department of MedicineJohns Hopkins School of MedicineBaltimoreUSA
  3. 3.Department of EpidemiologyUniversity of North Carolina at Chapel HillChapel HillUSA

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