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Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Young Jim, Xiao Yongling, Moodie Erica E M, Abrahamowicz Michal, Klein Marina B, Bernasconi Enos, Schmid Patrick, Calmy Alexandra, Cavassini Matthias, Cusini Alexia, Weber Rainer, Bucher Heiner C,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Journal of acquired immune deficiency syndromes (1999)
Volume (Issue) 69(4)
Page(s) 413 - 21
Title of proceedings Journal of acquired immune deficiency syndromes (1999)
DOI 10.1097/qai.0000000000000662

Open Access

URL http://dx.doi.org/10.7892/boris.68974
Type of Open Access Repository (Green Open Access)

Abstract

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. 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. 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. 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.
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