Jim Young1, Yongling Xiao, Erica E M Moodie, Michal Abrahamowicz, Marina B Klein, Enos Bernasconi, Patrick Schmid, Alexandra Calmy, Matthias Cavassini, Alexia Cusini, Rainer Weber, Heiner C Bucher. 1. *Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; †Analysis Group Inc, Montreal, QC, Canada; ‡Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; §Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada; ‖Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland; ¶Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; #Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland; **Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland; ††Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; ‡‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zürich, Zürich, Switzerland; and §§Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Abstract
BACKGROUND: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS: We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS: A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. CONCLUSIONS: Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.
BACKGROUND:Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS: We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS: A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. CONCLUSIONS:Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.
Authors: Huldrych F Günthard; Michael S Saag; Constance A Benson; Carlos del Rio; Joseph J Eron; Joel E Gallant; Jennifer F Hoy; Michael J Mugavero; Paul E Sax; Melanie A Thompson; Rajesh T Gandhi; Raphael J Landovitz; Davey M Smith; Donna M Jacobsen; Paul A Volberding Journal: JAMA Date: 2016-07-12 Impact factor: 56.272
Authors: Goodarz Danaei; Luis Alberto García Rodríguez; Oscar Fernández Cantero; Roger W Logan; Miguel A Hernán Journal: J Clin Epidemiol Date: 2018-04 Impact factor: 6.437
Authors: Joseph A Delaney; Robin M Nance; Bridget M Whitney; Heidi M Crane; Jessica Williams-Nguyen; Mathew J Feinstein; Robert C Kaplan; David B Hanna; Matthew J Budoff; Daniel R Drozd; Greer Burkholder; Michael J Mugavero; William C Mathews; Richard D Moore; Joseph J Eron; Peter W Hunt; Elvin Geng; Michael S Saag; Mari M Kitahata; Susan R Heckbert Journal: Epidemiology Date: 2019-01 Impact factor: 4.822