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J Acquir Immune Defic Syndr. 2015 Aug 1;69(4):413-21. doi: 10.1097/QAI.0000000000000662.

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

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  • 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.

PMID:
25932884
[PubMed - indexed for MEDLINE]
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