Abacavir exposure and cardiovascular risk factors in HIV-positive patients with coronary heart disease: a retrospective case–control study
Janine M. Trevillyan A C , Allen C. Cheng A B and Jennifer Hoy A BA Infectious Diseases Unit, The Alfred Hospital, 55 Commercial Road, Melbourne, Vic. 3004, Australia.
B Department of Infectious Diseases, Faculty of Medicine, Nursing and Health Science, Monash University, Vic. 3145, Australia.
C Corresponding author. Email: j.trevillyan@alfred.org.au
Sexual Health 10(2) 97-101 https://doi.org/10.1071/SH12081
Submitted: 1 June 2012 Accepted: 16 September 2012 Published: 21 December 2012
Abstract
Background: HIV-positive patients have an estimated twofold increased risk of acute myocardial infarction and coronary heart disease (CHD). While traditional cardiovascular risk factors and the effects of HIV and chronic inflammation all play a role, the contribution of long-term exposure to antiretroviral (ARV) agents is becoming clear. Methods: We performed a retrospective case–control study of HIV-positive patients seen from January 1996 to December 2009 to evaluate the impact of HIV suppression and exposure to specific ARVs on the incidence of CHD. Results: Cases (n = 68) were HIV-positive with evidence of CHD. Two age- and sex-matched HIV-positive controls (n = 136) without a diagnosis of CHD were assigned for each case. The cumulative incidence of CHD in the period covered by the study was 3.8%, with an incidence of 8.5 cases per 1000 patient-years of follow up. Cases had an increased likelihood of having hypertension (odds ratio (OR): 6.62, P < 0.001), a family history of CHD (OR: 5.82, P < 0.001), lower high-density lipoprotein levels (OR: 0.28, P = 0.025) and higher Framingham risk scores compared with controls. Following adjustment for traditional cardiovascular risk factors, the presence of CHD was significantly associated with the current use of abacavir (OR: 2.10, P = 0.03). Protease inhibitor therapy, HIV viral load and duration of known HIV infection were not predictive of CHD in our patient population. Conclusions: Our data add to the evidence that abacavir use is associated with CHD in HIV-positive patients in Australia.
Additional keywords: antiretroviral, cardiovascular disease, nucleoside analogue reverse transcriptase inhibitors.
References
[1] Klein D, Hurley LB, Quesenberry CP, Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002; 30 471–7.| Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmvVWisb0%3D&md5=b397201001b6ad4e52eeb21c136c1609CAS | 12154337PubMed |
[2] Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92 2506–12.
| Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotVyls7w%3D&md5=3b47bc7fb4940e8f98313db098e74293CAS | 17456578PubMed |
[3] Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE. Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav 2010; 14 824–35.
| Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation.Crossref | GoogleScholarGoogle Scholar | 18777131PubMed |
[4] Francisci D, Giannini S, Baldelli F, Leone M, Belfiori B, Guglielmini G, et al HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction. AIDS 2009; 23 589–96.
| HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction.Crossref | GoogleScholarGoogle Scholar | 19177019PubMed |
[5] Friis-Moller N, Sabin CA, Weber R, d’Arminio Monforte A, El-Sadr WM, Reiss P, et al Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003; 349 1993–2003.
| Combination antiretroviral therapy and the risk of myocardial infarction.Crossref | GoogleScholarGoogle Scholar | 14627784PubMed |
[6] Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann Intern Med 2006; 145 397–406.
| 16983127PubMed |
[7] Brothers CH, Hernandez JE, Cutrell AG, Curtis L, Ait-Khaled M, Bowlin SJ, et al Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009; 51 20–8.
| Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltVCkt7Y%3D&md5=b3f8b0fc394966befafcad9fbcbc2969CAS | 19282778PubMed |
[8] Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356 1723–35.
| Class of antiretroviral drugs and the risk of myocardial infarction.Crossref | GoogleScholarGoogle Scholar | 17460226PubMed |
[9] Hulten E, Mitchell J, Scally J, Gibbs B, Villines TC. HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies. Heart 2009; 95 1826–35.
| HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1MjisVamsg%3D%3D&md5=c7ff2371ed049b3c0eb76f837332d60cCAS | 19632982PubMed |
[10] Martin A, Bloch M, Amin J, Baker D, Cooper DA, Emery S, et al Simplification of antiretroviral therapy with tenofovir–emtricitabine or abacavir–lLamivudine: a randomized, 96-week trial. Clin Infect Dis 2009; 49 1591–601.
| Simplification of antiretroviral therapy with tenofovir–emtricitabine or abacavir–lLamivudine: a randomized, 96-week trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFChtL%2FI&md5=6599e51ebdd183c47a2a14d71287e36cCAS | 19842973PubMed |
[11] Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 31–41.
| Prediction of creatinine clearance from serum creatinine.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE28%2FnsF2isw%3D%3D&md5=10cca33639e2af2bacffa3c662d180c8CAS | 1244564PubMed |
[12] Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97 1837–47.
| Prediction of coronary heart disease using risk factor categories.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c3msVOjsA%3D%3D&md5=009a2caf7e186b12e907b8bdb687e446CAS | 9603539PubMed |
[13] Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, et al Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D : A : D study: a multi-cohort collaboration. Lancet 2008; 371 1417–26.
| Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D : A : D study: a multi-cohort collaboration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsFCisL8%3D&md5=d3b20144055f221afc7704c5c53ab883CAS | 18387667PubMed |
[14] Choi AI, Vittinghoff E, Deeks SG, Weekley CC, Li Y, Shlipak MG. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. AIDS 2011; 25 1289–98.
| Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXntlGrsrg%3D&md5=89f462acef003a2cd92eb7f975acdbfbCAS | 21516027PubMed |
[15] Obel N, Farkas DK, Kronborg G, Larsen CS, Pedersen G, Riis A, et al Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIV Med 2010; 11 130–6.
| Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitFCns78%3D&md5=580d2fc52b3d5376f168f57b18a73fcbCAS | 19682101PubMed |
[16] Bedimo RJ, Westfall AO, Drechsler H, Vidiella G, Tebas P. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 2011; 53 84–91.
| Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnsFWmtrk%3D&md5=dfcca85fae9d857f92380fe1bbb4f27cCAS | 21653308PubMed |
[17] Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case–control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med 2010; 170 1228–38.
| Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case–control study nested within the French Hospital Database on HIV ANRS cohort CO4.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVyltr7F&md5=78af6fd3ae84657446dc9585da286df0CAS | 20660842PubMed |
[18] Cruciani M, Zanichelli V, Serpelloni G, Bosco O, Malena M, Mazzi R, et al Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data. AIDS. 2011; 25 1993–2004.
| 1:CAS:528:DC%2BC3MXhtlSlu7nJ&md5=2e0a6e58eeadff2f59b2ee2866f05200CAS | 21716077PubMed |
[19] Satchell CS, O’Halloran JA, Cotter AG, Peace AJ, O’Connor EF, Tedesco AF, et al Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy. J Infect Dis 2011; 204 1202–10.
| Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SitLfM&md5=0bd4669e986926a39ae90ac8c42eec5fCAS | 21917893PubMed |
[20] Kristoffersen US, Kofoed K, Kronborg G, Benfield T, Kjaer A, Lebech AM. Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy. HIV Med 2009; 10 627–33.
| Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFKjtLbI&md5=6fd86f093d5e97c27218db7214ecc67fCAS | 19891054PubMed |
[21] The SMART/INSIGHT and the D : A : D Study Groups Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008; 22 F17–24.
| Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar | 18753925PubMed |
[22] Kenfield SA, Wei EK, Rosner BA, Glynn RJ, Stampfer MJ, Colditz GA. Burden of smoking on cause-specific mortality: application to the Nurses’ Health Study. Tob Control 2010; 19 248–54.
| Burden of smoking on cause-specific mortality: application to the Nurses’ Health Study.Crossref | GoogleScholarGoogle Scholar | 20501499PubMed |