Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population

Abstract

Background: To characterize the association of antiretroviral drug combinations on risk of cardiovascular events.

Methods: Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables.

Results: Over 164 059 person-years of follow-up, 934 patients had a cardiovascular event. Current exposure to abacavir, efavirenz, lamivudine, and zidovudine was significantly associated with increased risk of cardiovascular event, with odds ratios ranging from 1.40 to 1.53. Five combinations were significantly associated with increased risk of cardiovascular event, all of which involved lamivudine. One of these-efavirenz, lamivudine, and zidovudine-was the second most commonly used combination and was associated with a risk of cardiovascular event that is 1.60 times that of patients not currently exposed to the combination (odds ratio = 1.60, 95% confidence interval, 1.25-2.04).

Conclusions: In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.

Keywords: HIV; antiretroviral therapy; cardiovascular event; myocardial infarction.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Estimated effect of antiretroviral drug exposure on cardiovascular event. *Point estimates are interpreted as increase/decrease in odds of cardiovascular events given current exposure to therapy relative to not currently exposed to therapy. †Statistically significant according to the Bonferroni adjusted P value. Abbreviation: CI, confidence interval.

Figure 2.

Estimated effect of combination antiretroviral exposure on cardiovascular event. *Point estimates are interpreted as increase/decrease in odds of cardiovascular events given current exposure to therapy relative to not currently exposed to therapy. †Statistically significant according to the Bonferroni adjusted P value. Abbreviation: CI, confidence interval.