Abstract
OBJECTIVE: Compare all-cause mortality between Indigenous participants and participants of other ethnicities living with HIV initiating combination antiretroviral therapy (cART) in an interprovincial multi-site cohort.
METHODS: The Canadian Observational Cohort is a collaboration of 8 cohorts of treatment-naïve persons with HIV initiating cART after January 1, 2000. Participants were followed from the cART initiation date until death or last viral load (VL) test date on or before December 31, 2012. Cox proportional hazard models were used to estimate the effect of ethnicity on time until death after adjusting for age, gender, injection drug use, being a man who has sex with men, hepatitis C, province of origin, baseline VL and CD4 count, year of cART initiation and class of antiretroviral medication.
RESULTS: The study sample consisted of 7080 participants (497 Indigenous, 2471 Caucasian, 787 African/Caribbean/Black (ACB), 629 other, and 2696 unknown ethnicity). Most Indigenous persons were from British Columbia (BC) (83%), with smaller numbers from Ontario (13%) and Québec (4%). During the study period, 714 (10%) participants died. The five-year survival probability was lower for Indigenous persons (0.77) than for Caucasian (0.94), ACB (0.98), other ethnicities (0.96) and unknown ethnicities (0.85) (p < 0.0001). In an adjusted proportional hazard model for which missing data were imputed, Indigenous persons were more likely to die than Caucasian participants (hazard ratio = 2.69, p < 0.0001).
CONCLUSION: The mortality rate for Indigenous persons was higher than for other ethnicities and is largely reflective of the BC population. Addressing treatment challenges and identifying HIV- and non-HIV-related causes for mortality among Indigenous persons is required to optimize their clinical management.
Key Words: Indigenous, mortality, HIV, cohort study, combination antiretroviral therapy
Résumé
OBJECTIF: Comparer la mortalité toutes causes confondues de participants autochtones et de participants d’autres origines ethniques vivant avec le VIH ayant entrepris un traitement antirétroviral d’association (TARa) dans une cohorte interprovinciale multi-sites.
MÉTHODE: Le centre de recherche collaborative CANOC (Canadian HIV Observational Cohort Collaboration) est une collaboration impliquant 8 cohortes de patients atteints du VIH n’ayant jamais reçu de traitement qui ont amorcé un TARa après le 1er janvier 2000. Ces patients ont été suivis depuis la date de début de leur TARa jusqu’à leur décès ou à la date de la dernière mesure de leur charge virale, soit au plus tard le 31 décembre 2012. À l’aide de modèles à risques proportionnels de Cox, nous avons estimé l’effet de l’ethnicité sur la longévité après avoir tenu compte de l’âge, du sexe, de l’utilisation de drogues par injection, du fait d’être un homme ayant des relations sexuelles avec des hommes, de l’hépatite C, de la province d’origine, de la charge virale et de la numération des lymphocytes CD4 de référence, de l’année de début du TARa et de la classe d’antirétroviraux.
RÉSULTATS: L’échantillon de l’étude comprenait 7 080 participants (497 Autochtones, 2 471 Blancs, 787 personnes des communautés africaine, caribéenne et noire [ACN], 629 personnes d’autres origines ethniques, et 2 696 personnes d’ethnicité inconnue). La plupart des Autochtones venaient de la Colombie-Britannique (C.-B.) (83 %) et dans de moindres proportions de l’Ontario (13 %) et du Québec (4 %). Durant la période de l’étude, 714 participants (10 %) sont décédés. La probabilité de survie après cinq ans a été plus faible chez les Autochtones (0,77) que chez les Blancs (0,94), les participants des communautés ACN (0,98), les participants d’autres origines ethniques (0,96) et les participants d’ethnicité inconnue (0,85) (p < 0,0001). Avec un modèle à risques proportionnels ajusté pour lequel les données manquantes ont été imputées, les Autochtones ont été plus susceptibles de mourir que les Blancs (coefficient de danger = 2,69, p<0,0001).
CONCLUSION: Le taux de mortalité des Autochtones était plus élevé que celui des participants d’autres origines ethniques et reflète dans une large mesure la population de la C.-B. Il est nécessaire d’aborder les défis thérapeutiques et de déterminer les causes de mortalité liées et non liées au VIH chez les Autochtones pour optimiser leur prise en charge clinique.
Mots Clés: Autochtones, mortalité, VIH, étude de cohorte, traitement antirétroviral d’association
Footnotes
Acknowledgements: First and foremost, the authors thank all of the Building Bridges participants for sharing their experiences and allowing for this project to be driven by community interests. The authors also thank all the participants for allowing their information to be a part of the CANOC collaboration [See ARTICLE TOOLS section on journal site for Supplementary Appendix: CANOC].
Sources of Funding: CANOC is funded by the Canadian Institutes of Health Research (CIHR) through a Centres for HIV/AIDS Population Health and Health Services Research Grant [CIHR 02684], Operating Grants HIV/AIDS Priority Announcement [CIHR 134047] and Population and Public Health [CIHR 136882], and by the CIHR Canadian HIV Trials Network (CTN 242) as well as a Foundation Grant (Expansion of Antiretroviral Therapy and its Impact on Vulnerable Populations in Canada and Global Settings [CIHR 143342]). Building Bridges is supported by a CIHR Catalyst Grant. JR is supported through an Ontario HIV Treatment Network (OHTN) Chair in Biostatistics. ANB and TA are supported by CIHR New Investigator Awards and ACB was supported by a CIHR Fellowship Award at the time of this project. CC is supported through an Applied HIV Research Chair from the OHTN. DJ is supported by the Clinician Investigator Program at the University of British Columbia. MK is supported by a Chercheur National Career Award from the Fonds de Recherche Québec-Santé (FRQ-S). RSH is supported by a University Professorship at Simon Fraser University.
Conflict of Interest: CC has served on advisory boards for Abbvie and Gilead Sciences. MBK reports grants from Merck and ViiV Healthcare and personal fees for consultancy from ViiV Healthcare, Bristol-Meyers Squibb, and Merck. ML has served on advisory boards and spoken at CME events for Viiv Healthcare, Abbvie, Merck Canada Inc. and Gilead Sciences. NM has been a speaker for Bristol-Meyers Squibb, Merck, and ViiV Healthcare. JSGM is supported with grants paid to his institution by the British Columbia Ministry of Health and by the US National Institutes of Health (R01DA036307). He has also received limited unrestricted funding, paid to his institution, from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. JR is co-investigator on four projects, outside the submitted work, with in-kind contributions or financial support from Merck and Gilead Sciences. AR has served on medical advisory boards for ViiV Healthcare, Merck and Gilead Sciences. RSH reports personal fees from Gilead Sciences. For the remaining authors, no conflicts of interest were declared.
Building Bridges research team
Building Bridges consists of a research team in Toronto, Ontario and Vancouver, British Columbia. The nominated principal investigator was Mark Hull, located in Vancouver, and the Vancouver research team consisted of co-investigators Robert Hogg, Denise Jaworsky, Janet Raboud and Elizabeth Benson; additional research team members were Susan Giles, Evanna Brennan and Hasina Samji. Denise Jaworsky coordinated the project in Vancouver under the guidance of the Vancouver research team along with the Indigenous community advisory committee: Carol Kellman, Valerie Nicholson, Elder Doris Xele’milh Paul, Elder Roberta Price, and Flo Ranville. Mona Loutfy was the principal investigator in Toronto and the principal community investigator was Renée Masching. The Toronto research team consisted of co-investigators Anita C. Benoit, Doe O’Brien-Teengs and Janet Raboud. Jaime Younger conducted the data analyses for the Toronto Research team. Anita Benoit assumed direction of the project in Toronto under the guidance and expertise of the Toronto research team and assistance from Kerrigan Beaver, which includes the Indigenous community advisory committee, some of whom have requested to be listed: Kerrigan Beaver, Randy Jackson, Michael Keshane, Tony Nobis, Earl Nowgesic, Tera Tynes, Tonie Walsh, Spiritual Leader Wanda Whitebird and Art Zoccole. Toronto research team members substantially contributed to the conception and design, or acquisition of data, or analysis and interpretation of data.
†CANOC investigators
The CANOC principal investigators consist of Centre investigator Robert Hogg and Centre site investigators Ann N. Burchell, Curtis Cooper, Deborah Kelly, Marina Klein, Mona Loutfy, Nima Machouf, Julio Montaner, Janet Raboud, Chris Tsoukas, Stephen Sanche, Alexander Wong, Ahmed Bayoumi, Tony Antoniou, Bohdan Nosyk and Mark Hull. CANOC co-investigators include Angela Cescon, Michelle Cotterchio, Charlie Goldsmith, Silvia Guillemi, P. Richard Harrigan, Marianne Harris, Sean Hosein, Sharon Johnston, Claire Kendall, Clare Liddy, Viviane Lima, David Marsh, David Moore, Alexis Palmer, Sophie Patterson, Peter Phillips, Anita Rachlis, Sean B. Rourke, Hasina Samji, Marek Smieja, Benoit Trottier, Mark Wainberg [Dr. Mark Wainberg passed away after the manuscript was accepted for publication] and Sharon Walmsley.
References
- 1.Tjepkema M, Wilkins R, Senecal S, Guimond E, Penney C. Mortality of urban Aboriginal adults in Canada, 1991–2001. Chronic Dis Can. 2010;31(1):4–21. [PubMed] [Google Scholar]
- 2.Frohlich KL, Ross N, Richmond C. Health disparities in Canada today: Some evidence and a theoretical framework. Health Policy. 2006;79(2–3):132–43. doi: 10.1016/j.healthpol.2005.12.010. [DOI] [PubMed] [Google Scholar]
- 3.MacMillan HL, MacMillan AB, Offord DR, Dingle JL. Aboriginal health. CMAJ. 1996;155(11):1569–78. [PMC free article] [PubMed] [Google Scholar]
- 4.Martens PJ, Sanderson D, Jebamani LS. Mortality comparisons of First Nations to all other Manitobans: A provincial population-based look at health inequalities by region and gender. Can J Public Health. 2005;96(1):S33–38. doi: 10.1007/BF03405314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Trovato F. Canadian Indian mortality during the 1980s. Soc Biol. 2000;47(1–2):135–45. doi: 10.1080/19485565.2000.9989015. [DOI] [PubMed] [Google Scholar]
- 6.Wilkins R, Tjepkema M, Mustard C, Choiniere R. The Canadian census mortality follow-up study, 1991 through 2001. Health Rep. 2008;19(3):25–43. [PubMed] [Google Scholar]
- 7.Wilkins R, Uppal S, Fines P, Senecal S, Guimond E, Dion R. Life expectancy in the Inuit-inhabited areas of Canada, 1989 to 2003. Health Rep. 2008;19(1):7–19. [PubMed] [Google Scholar]
- 8.Park J, Tjepkema M, Goedhuis N, Pennock J. Avoidable mortality among First Nations adults in Canada: A cohort analysis. Health Rep. 2015;26(8):10–16. [PubMed] [Google Scholar]
- 9.Population-Specific HIV/AIDS Status Report–Aboriginal Peoples. Public Health Agency of Canada, 2010. Available at: http://www.phac-aspc.gc.ca/aids-sida/publication/ps-pd/aboriginal-autochtones/pdf/pshasrap-revspda-eng.pdf (Accessed February 21, 2014).
- 10.Samji H, Cescon A, Hogg RS, Modur SP, Althoff KN, Buchacz K, et al. Closing the gap: Increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS ONE. 2013;8(12):e81355. doi: 10.1371/journal.pone.0081355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Antiretroviral Therapy Cohort Collaboration. Influence of geographical origin and ethnicity on mortality in patients on antiretroviral therapy in Canada, Europe, and the United States. Clin Infect Dis. 2013;56(12):1800–9. doi: 10.1093/cid/cit111. [DOI] [PubMed] [Google Scholar]
- 12.Martin LJ, Houston S, Yasui Y, Wild TC, Saunders LD. All-cause and HIV-related mortality rates among HIV-infected patients after initiating highly active antiretroviral therapy: The impact of Aboriginal ethnicity and injection drug use. Can J Public Health. 2011;102(2):90–96. doi: 10.1007/BF03404154. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lima VD, Kretz P, Palepu A, Bonner S, Kerr T, Moore D, et al. Aboriginal status is a prognostic factor for mortality among antiretroviral naive HIV-positive individuals first initiating HAART. AIDS Res Ther. 2006;3:14. doi: 10.1186/1742-6405-3-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Patterson S, Cescon A, Samji H, Chan K, Zhang W, Raboud J, et al. Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada. BMC Infect Dis. 2015;15:274. doi: 10.1186/s12879-015-0969-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Negin J, Aspin C, Gadsden T, Reading C. HIV among Indigenous peoples: A review of the literature on HIV-related behaviour since the beginning of the epidemic. AIDS Behav. 2015;19(9):1720–34. doi: 10.1007/s10461-015-1023-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Benoit AC, Jaworsky D, Beaver K, Benson E, Jackson R, Brennan E, et al., editors. Building Bridges: A model for community engagement in epidemiology research; 2015. [Google Scholar]
- 17.Nowgesic E. What Does it Mean to Have an Aboriginal Health Epidemiology Model? Building Bridges Final Gathering. 2015. [Google Scholar]
- 18.Denzin NK, Lincoln YS. Introduction: Critical Methodologies and Indigenous Inquiry. Thousand Oaks, CA: Sage; 2008. Handbook of critical and Indigenous methodologies; pp. 1–20. [Google Scholar]
- 19.Palmer AK, Klein MB, Raboud J, Cooper C, Hosein S, Loutfy M, et al. Cohort profile: The Canadian Observational Cohort collaboration. Int J Epidemiol. 2011;40(1):25–32. doi: 10.1093/ije/dyp393. [DOI] [PubMed] [Google Scholar]
- 20.Robins JM, Finkelstein DM. Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests. Biometrics. 2000;56(3):779–88. doi: 10.1111/j.0006-341X.2000.00779.x. [DOI] [PubMed] [Google Scholar]
- 21.Bartlett JW, Taylor JMG. Missing covariates in competing risks analysis. Biostatistics. 2016;17(4):751–63. doi: 10.1093/biostatistics/kxw019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Wood E, Montaner JS, Tyndall MW, Schechter MT, O’Shaughnessy MV, Hogg RS. Prevalence and correlates of untreated human immunodeficiency virus type 1 infection among persons who have died in the era of modern antiretroviral therapy. J Infect Dis. 2003;188(8):1164–70. doi: 10.1086/378703. [DOI] [PubMed] [Google Scholar]
- 23.Mocroft A, Gatell J, Reiss P, Ledergerber B, Kirk O, Vella S, et al. Causes of death in HIV infection: The key determinant to define the clinical response to anti-HIV therapy. AIDS. 2004;18(17):2333–37. doi: 10.1097/00002030-200411190-00018. [DOI] [PubMed] [Google Scholar]
- 24.Rodriguez-Arenas MA, Jarrin I, del Amo J, Iribarren JA, Moreno S, Viciana P, et al. Delay in the initiation of HAART, poorer virological response, and higher mortality among HIV-infected injecting drug users in Spain. AIDS Res Hum Retroviruses. 2006;22(8):715–23. doi: 10.1089/aid.2006.22.715. [DOI] [PubMed] [Google Scholar]
- 25.Bouhnik AD, Chesney M, Carrieri P, Gallais H, Moreau J, Moatti JP, et al. Nonadherence among HIV-infected injecting drug users: The impact of social instability. J Acquir Immune Defic Syndr. 2002;31(3):S149–53. doi: 10.1097/00126334-200212153-00013. [DOI] [PubMed] [Google Scholar]
- 26.Minuk GY, O’Brien M, Hawkins K, Emokpare D, McHattie J, Harris P, et al. Treatment of chronic hepatitis C in a Canadian Aboriginal population: Results from the PRAIRIE study. Can J Gastroenterol. 2013;27(12):707–10. doi: 10.1155/2013/963694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Dawood M, Smart G, Wood M, Wu HX, Paton S, Wu J. Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada–a public health laboratory study. Can J Microbiol. 2006;52(10):999–1005. doi: 10.1139/w06-056. [DOI] [PubMed] [Google Scholar]
- 28.Braitstein P, Yip B, Montessori V, Moore D, Montaner JS, Hogg RS. Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIV-positive patients. CMAJ. 2005;173(2):160–64. doi: 10.1503/cmaj.045202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Kolahdooz F, Nader F, Yi KJ, Sharma S. Understanding the social determinants of health among Indigenous Canadians: Priorities for health promotion policies and actions. Glob Health Action. 2015;8:27968. doi: 10.3402/gha.v8.27968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Mitrou F, Cooke M, Lawrence D, Povah D, Mobilia E, Guimond E, et al. Gaps in Indigenous disadvantage not closing: A census cohort study of social determinants of health in Australia, Canada, and New Zealand from 1981–2006. BMC Public Health. 2014;14:201. doi: 10.1186/1471-2458-14-201. [DOI] [PMC free article] [PubMed] [Google Scholar]