Abstract
Background: Aboriginals are over-represented in Canada’s HIV epidemic and are commonly infected with HIV via injection drug use (IDU); however, little is known about the impact of Aboriginal ethnicity on mortality after starting highly active antiretroviral therapy (HAART). Therefore, we compared mortality rates between Aboriginal and non-Aboriginal HIV patients and between IDU and non-IDU HIV patients after they initiated HAART.
Methods: We conducted a retrospective cohort study of antiretroviral-naïve patients starting HAART January 1999–June 2005 (baseline), followed until December 2005. We constructed two Cox proportional hazards models, one to estimate all-cause and one to estimate HIV-related mortality hazard ratios (HRs), considering sex, and baseline age, CD4 cell count, HIV RNA level, calendar year, and HAART regimen as potential confounders.
Results: The 548 study patients were followed for 1,889.8 person-years; 194 (35%) were Aboriginal, 255 (46%) were IDUs. We observed 55 deaths; 47% were HIV-related. In multivariable models, Aboriginals experienced higher all-cause (HR=1.85, 95% CI=1.05-3.26, p=0.034) and HIV-related (HR=3.47, 95% CI=1.36-8.83, p=0.009) mortality rates compared to non-Aboriginals; and, compared to patients with other exposures, IDUs experienced higher all-cause (HR=2.45, 95% CI=1.31-4.57, p=0.005) but similar HIV-related (p=0.27) mortality rates.
Conclusions: Compared to non-Aboriginals, Aboriginal HIV patients suffer higher all-cause and HIV-related mortality rates after starting HAART. The strongest and most significant predictor of higher all-cause mortality was IDU. Future research should examine reasons for the observed poorer survival of Aboriginal and IDU HIV patients after initiating HAART to develop interventions to improve the prognosis for these vulnerable populations.
Key Words: Antiretroviral therapy, highly active, mortality, Aboriginal populations, intravenous drug use
Résumé
Contexte: Les Autochtones sont surreprésentés dans l’épidémie de VIH qui sévit au Canada, le plus souvent en raison de l’utilisation de drogues par injection (UDI); pourtant, on sait peu de choses sur l’impact de l’ethnicité autochtone sur la mortalité après le début d’une thérapie antirétrovirale hautement active (TAHA). C’est pourquoi nous avons comparé les taux de mortalité de patients autochtones et non autochtones atteints du VIH et ceux d’UDI et de non-UDI atteints du VIH après le début d’une TAHA.
Méthode: Nous avons mené une étude de cohortes rétrospective auprès de patients naïfs de traitement antirétroviral ayant entamé une TAHA entre janvier 1999 et juin 2005 (groupe de référence), que nous avons suivis jusqu’en décembre 2005. Nous avons construit deux modèles de Cox (modèles des risques proportionnels), l’un pour estimer les coefficients de danger (QD) pour toutes les causes de mortalité et l’autre pour la mortalité liée au VIH, en tenant compte des facteurs confusionnels possibles (sexe, âge au départ, numération des lymphocytes CD4, niveaux d’ARN VIH, année civile et régime TAHA).
Résultats: Les 548 patients à l’étude ont été suivis sur 1 889,8 personnes-années; 194 (35 %) étaient Autochtones, et 255 (46 %) étaient des UDI. Nous avons observé 55 décès, dont 47 % liés au VIH. Dans les modèles multivariés, les Autochtones affichaient des taux supérieurs pour la mortalité toutes causes confondues (QD=1,85, IC de 95 %=1,05-3,26, p=0,034) et la mortalité liée au VIH (QD=3,47, IC de 95 %=1,36-8,83, p=0,009) comparativement aux Non-Autochtones. Par rapport aux patients ayant d’autres expositions, les UDI affichaient des taux supérieurs de mortalité toutes causes confondues (QD=2,45, IC de 95 %=1,31-4,57, p=0,005), mais leurs taux de mortalité liée au VIH étaient semblables (p=0,27).
Conclusion: À comparer aux Non-Autochtones, les patients autochtones atteints du VIH ont des taux supérieurs de mortalité toutes causes confondues et de mortalité liée au VIH après le début d’une TAHA. La variable prédictive la plus forte et la plus significative de la mortalité toutes causes confondues était le statut d’UDI. Dans les futurs travaux de recherche, il faudrait se pencher sur les raisons des moins bons taux de survie observés chez les patients autochtones et les UDI atteints du VIH après le début d’une TAHA afin d’élaborer des interventions susceptibles d’améliorer le pronostic de ces populations vulnérables.
Mots Clés: thérapie antirétrovirale hautement active, mortalité, population d’origine amérindienne, toxicomanie intraveineuse
Footnotes
Previous Presentations: A previous version of this analysis was presented in part at the 16th Annual Canadian Conference on HIV/AIDS Research, c]Toronto, s]ONtario, Canada April 26–29, 2007 and this work was presented at the XVII International AIDS Conference, Mexico City, Mexico, August 3–8, 2008. This work was also included as a chapter in LJ Martin’s PhD thesis (2009).
Conflict of Interest: None to declare.
References
- 1.Palella FJ, Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338(13):853–60. doi: 10.1056/NEJM199803263381301. [DOI] [PubMed] [Google Scholar]
- 2.Hogg RS, Yip B, Kully C, Craib K O, Shaughnessy MV, Schechter MT, et al. Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens. CMAJ. 1999;160(5):659–65. [PMC free article] [PubMed] [Google Scholar]
- 3.CASCADE Collaboration. Determinants of survival following HIV-1 seroconversion after the introduction of HAART. Lancet. 2003;362(9392):1267–74. doi: 10.1016/S0140-6736(03)14570-9. [DOI] [PubMed] [Google Scholar]
- 4.Voirin N, Trépo C, Miailhes P, Touraine JL, Chidiac C, Peyramond D, et al. Survival in HIV-infected patients is associated with hepatitis C virus infection and injecting drug use since the use of highly active antiretroviral therapy in the Lyon observational database. J Viral Hepat. 2004;11(6):559–62. doi: 10.1111/j.1365-2893.2004.00544.x. [DOI] [PubMed] [Google Scholar]
- 5.Lima VD, Kretz P, Palepu A, Bonner S, Kerr T, Moore D, et al. Aboriginal status is a prognostic factor for mortality among antiretroviral naïve 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]
- 6.Public Health Agency of Canada. HIV/AIDS Epi Updates, November 2007. 2007. [Google Scholar]
- 7.The Antiretroviral Therapy Cohort Collaboration. Importance of baseline prognostic factors with increasing time since initiation of highly active antiretroviral therapy: Collaborative analysis of cohorts of HIV-1-infected patients. J Acquir Immune Defic Syndr. 2007;46(5):607–15. doi: 10.1097/QAI.0b013e31815b7dba. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.May M, Sterne JAC, Sabin C, Costagliola D, Justice AC, Thiébaut R, et al. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: Collaborative analysis of prospective studies. AIDS. 2007;21(9):1185–97. doi: 10.1097/QAD.0b013e328133f285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.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]
- 10.Martin LJ. Outcomes of antiretroviral therapy in northern Alberta: The impact of Aboriginal ethnicity and injection drug use [thesis] Edmonton, AB: University of Alberta; 2009. [Google Scholar]
- 11.Public Health Agency of Canada. HIVAIDS in Canada. Surveillance Report to December 31, 2006. 2007. [Google Scholar]
- 12.World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 2007. [Google Scholar]
- 13.Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: New representations of old estimators. Stat Med. 1999;18(6):695–706. doi: 10.1002/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
- 14.Hogg RS, Heath K, Bangsberg D, Yip B, Press N, O’Shaughnessy MV, et al. Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS. 2002;16(7):1051–58. doi: 10.1097/00002030-200205030-00012. [DOI] [PubMed] [Google Scholar]
- 15.Lucas GM, Cheever LW, Chaisson RE, Moore RD. Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 2001;27(3):251–59. doi: 10.1097/00042560-200107010-00006. [DOI] [PubMed] [Google Scholar]
- 16.Lucas GM, Griswold M, Gebo KA, Keruly J, Chaisson RE, Moore RD. Illicit drug use and HIV-1 disease progression: A longitudinal study in the era of highly active antiretroviral therapy. Am J Epidemiol. 2006;163(5):412–20. doi: 10.1093/aje/kwj059. [DOI] [PubMed] [Google Scholar]
- 17.Hendershot CS, Stoner SA, Pantalone DW, Simoni JM. Alcohol use and antiretroviral adherence: Review and meta-analysis. J Acquir Immune Defic Syndr. 2009;52(2):180–202. doi: 10.1097/QAI.0b013e3181b18b6e. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Clarke DE, Colantonio A, Rhodes AE, Escobar M. Pathways to suicidality across ethnic groups in Canadian adults: The possible role of social stress. Psychol Med. 2008;38(3):419–31. doi: 10.1017/S0033291707002103. [DOI] [PubMed] [Google Scholar]
- 19.Bouhnik A-D, 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(Suppl3):S149–S153. doi: 10.1097/00126334-200212153-00013. [DOI] [PubMed] [Google Scholar]
- 20.Kleeberger CA, Phair JP, Strathdee SA, Detels R, Kingsley L, Jacobson LP. Determinants of heterogeneous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2001;26(1):82–92. doi: 10.1097/00126334-200101010-00012. [DOI] [PubMed] [Google Scholar]
- 21.Spire B, Duran S, Souville M, Leport C, Raffi F, Moatti JP, et al. Adherence to highly active antiretroviral therapies (HAART) in HIV-infected patients: From a predictive to a dynamic approach. Soc Sci Med. 2002;54(10):1481–96. doi: 10.1016/S0277-9536(01)00125-3. [DOI] [PubMed] [Google Scholar]
- 22.Health Canada. A Statistical Profile on the Health of First Nations in Canada for the Year 2000. 2005. p. 123. [Google Scholar]
- 23.Miller CL, Spittal PM, Wood E, Chan K, Schechter MT, Montaner JSG, et al. Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian populations. AIDS Care. 2006;18(8):968–76. doi: 10.1080/09540120500481480. [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.Dray-Spira R, Spire B, Heard I, Lert F, The Vespa Study Group Heterogeneous response to HAART across a diverse population of people living with HIV: Results from the ANRS-EN12-VESPA Study. AIDS. 2007;21(Suppl1):S5–S12. doi: 10.1097/01.aids.0000255079.39352.9b. [DOI] [PubMed] [Google Scholar]
- 26.Strader DB. Coinfection with HIV and hepatitis C virus in injection drug users and minority populations. Clin Infect Dis. 2005;41(Suppl1):S7–S13. doi: 10.1086/429489. [DOI] [PubMed] [Google Scholar]
- 27.Braitstein P, Yip B, Montessori V, Moore D, Montaner JSG, Hogg RS. Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIVpositive patients. CMAJ. 2005;173(2):160–64. doi: 10.1503/cmaj.045202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Gossop M, Stewart D, Treacy S, Marsden J. A prospective study of mortality among drug misusers during a 4-year period after seeking treatment. Addiction. 2002;97(1):39–47. doi: 10.1046/j.1360-0443.2002.00079.x. [DOI] [PubMed] [Google Scholar]
- 29.Alcoba M, Cuevas MJ, Perez-Simon MR, Mostaza JL, Ortega L, Ortiz d U J, et al. Assessment of adherence to triple antiretroviral treatment including indinavir: Role of the determination of plasma levels of indinavir. J Acquir Immune Defic Syndr. 2003;33(2):253–58. doi: 10.1097/00126334-200306010-00022. [DOI] [PubMed] [Google Scholar]
- 30.Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: Methods, validity, and applications. J Clin Epidemiol. 1997;50(1):105–16. doi: 10.1016/S0895-4356(96)00268-5. [DOI] [PubMed] [Google Scholar]
- 31.Low-Beer S, Yip B, O’Shaughnessy MV, Hogg RS, Montaner JS, Low-Beer S, et al. Adherence to triple therapy and viral load response. J Acquir Immune Defic Syndr. 2000;23(4):360–61. doi: 10.1097/00126334-200004010-00016. [DOI] [PubMed] [Google Scholar]
- 32.Liu H, Golin CE, Miller LG, Hays RD, Beck CK, Sanandaji S, et al. A comparison study of multiple measures of adherence to HIV protease inhibitors. [erratum appears in Ann Intern Med 2002;136(2):175] Ann Intern Med. 2001;134(10):968–77. doi: 10.7326/0003-4819-134-10-200105150-00011. [DOI] [PubMed] [Google Scholar]
- 33.Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. [erratum appears in Ann Intern Med 2002;136(3):253] Ann Intern Med. 2000;133(1):21–30. doi: 10.7326/0003-4819-133-1-200007040-00004. [DOI] [PubMed] [Google Scholar]