Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

Margalida Rotger, Tracy R. Glass, Thomas Junier, Jens Lundgren, James D. Neaton, Estella S. Poloni, Angélique B. Van 'T Wout, Rubin Lubomirov, Sara Colombo, Raquel Martinez, Andri Rauch, Huldrych F. Günthard, Jacqueline Neuhaus, Deborah Wentworth, Danielle Van Manen, Luuk A. Gras, Hanneke Schuitemaker, Laura Albini, Carlo Torti, Lisa P. JacobsonXiuhong Li, Lawrence A. Kingsley, Federica Carli, Giovanni Guaraldi, Emily S. Ford, Irini Sereti, Colleen Hadigan, Esteban Martinez, Mireia Arnedo, Lander Egaña-Gorroño, Jose M. Gatell, Matthew Law, Courtney Bendall, Kathy Petoumenos, Jürgen Rockstroh, Jan Christian Wasmuth, Kabeya Kabamba, Marc Delforge, Stephane De Wit, Florian Berger, Stefan Mauss, Mariana De Paz Sierra, Marcelo Losso, Waldo H. Belloso, Maria Leyes, Antoni Campins, Annalisa Mondi, Andrea De Luca, Ignacio Bernardino, Mónica Barriuso-Iglesias, Ana Torrecilla-Rodriguez, Juan Gonzalez-Garcia, José R. Arribas, Iuri Fanti, Silvia Gel, Jordi Puig, Eugenia Negredo, Mar Gutierrez, Pere Domingo, Julia Fischer, Gerd Fätkenheuer, Carlos Alonso-Villaverde, Alan MacKen, James Woo, Tara McGinty, Patrick Mallon, Alexandra Mangili, Sally Skinner, Christine A. Wanke, Peter Reiss, Rainer Weber, Heiner C. Bucher, Jacques Fellay, Amalio Telenti, Philip E. Tarr

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10 -4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalClinical Infectious Diseases
Volume57
Issue number1
DOIs
StatePublished - Jul 2013

Bibliographical note

Funding Information:
Financial support. This work was supported by the Swiss National Science Foundation (SNF; project 324730_127631/1), the Swiss HIV Cohort Study (SNF grant 33CS30_134277, SHCS project 599), an INFEC-TIGEN grant from the Universities of Geneva and Lausanne (to P. E. T.), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, and unrestricted grants from Gilead Sciences and Merck Sharp & Dohme Switzerland to the SHCS research foundation. The IdiPAZ Biobank is supported by Instituto de Salud Carlos III, Spanish Health Ministry (RETIC RD09/0076/00073) and Farmaindustria, through the Cooperation Program in Clinical and Translational Research of the Community of Madrid Red de Investigación en SIDA grant (ISCIII-RETIC RD06/0006/1017, ISCIII-MA06/0164).

Funding Information:
Potential conflicts of interest. A. B. W. currently is Manager Scientific Affairs with the Crucell Vaccine Institute; the present work was initiated while she was working full-time at the Academic Medical Center (AMC) at University of Amsterdam and has been completed through her continued affiliation with the AMC. H. F. G. has been adviser and/or consultant for GlaxoSmithKline (GSK), Abbott, Gilead, Novartis, Boehringer Ingelheim, Roche, Tibotec, Pfizer, and Bristol-Myers Squibb (BMS), and his institution has received funding from Roche, Abbott, BMS, Gilead, Astra-Zeneca, GlaxoSmithKline, and MSD. C. T. has received lecture fees from Viiv and travel expenses from Viiv and Gilead. L. J. has been a consultant for BMS. E. M. has received consultancy and lecture fees from Abbott, BI, BMS, Gilead, GSK, MSD, Theratechnologies, Tibotec, and ViiV. J. R. has received advisory/lecture/consulting fees from Abbott, Bionor, BI, BMS, Gilead, GSK, Merck, Novartis, Janssen, Pfizer, Vertex, and ViiV and his institution has received funding from Abbott, MSD, and Roche. J.-C. W. has received advisory/lecture fees from Abbott, BMS, BI, Pfizer, and Tibotec and travel fees from Gilead. S. D. has received advisory fees from BMS and his institution has received consultancy fees from Viiv and travel fees from Janssen, Viiv, Gilead, Abbvie, and BMS. S. M. has received consulting/advisory fees from AbbVie, BI, BMS, Gilead, Janssen, and Roche and travel grants from the same companies plus MSD. J. G. has received consulting fees and his institution has received funding from Gilead, Abbott, BMS, MSD, and Janssen. The institution of C. B., K. P., and M. L. has received funding from BI, BMS, Gilead, GSK, Janssen, MSD, Pfizer, and Roche. M. L. has received payments for serving on data and safety monitoring boards for Sirtex Pty Ltd. A. D. has received advisory/consultant fees from Janssen, ViiV, Abbott, and Gilead, travel grants from ViiV and Abbott, and funding from ViiV and Janssen. A. D. has received advisory fees from Gilead and Viiv, consulting fees from Janssen and Abbott, and travel grants from Abbott and Viiv, and his institution has received funding from Viiv and Janssen. I. B. has received research funding and consulting/ lecture fees from Abbott, Gilead, BMS, ViiV, and Janssen. J. G. G. has received consultancy fees from Abbott, Janssen, MSD, BMS, Gilead, ViiV, and Roche. J. R. A. has received advisory/speaker fees and grant support from Viiv, Tibotec, Janssen, Abbott, BMS, Gilead, and MSD. E. N. has received consultant fees from Gilead, BI, MSD, Abbott, Tibotec, GSK, and BMS. P. D. has received advisory, consultant, and/or lecture fees and has been a data safety monitoring board member for Gilead, Abbott, Janssen, BI, BMS, MSD, Theratechnologies, ViiV, and Ferrer. G. F. has received consultancy/lecture fees and funding from AbbVie, Janssen, Gilead, BMS, MSD, Pfizer, Roche, and ViiV. A. M. currently is Medical Director, HIV/ Endocrinology with EMD Serono; the present work was initiated while she was working full-time at Tufts University and has been completed through her continued affiliation with Tufts. R. W.’s institution has received travel grants from Abbott, BI, BMS, Gilead, GSK, MSD, Pfizer, Roche, TRB Chemedica, and Tibotec. P. R. has been adviser for GSK, Gilead, and Janssen, and his institution has received funding and/or travel support from Gilead, ViiV, MSD, Janssen, BMS, and BI. He has served on data safety monitoring boards and endpoint adjudication committees for Janssen, and his institution has received honoraria for development of educational presentations from Gilead. H. C. B.’s institution has received travel grants, honoraria, and unrestricted research grants from GSK, BMS, Gilead, Janssen, Roche, Abbott, Tibotec, BI, and ViiV and is supported by unrestricted grants from Santésuisse and the Gottfried and Julia Bangerter-Rhyner-Foundation. P. E. T. has received advisory fees from Janssen, consultancy fees from Gilead, and honoraria from Viiv, and his institution has received advisory fees from Gilead and MSD, honoraria from Viiv, and travel expenses from MSD and Viiv. All other authors report no potential conflicts.

Keywords

  • HIV infection
  • antiretroviral therapy
  • coronary artery disease
  • genetics
  • traditional risk factors

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