Some antiretroviral drugs used to treat HIV associated with an elevated risk of myocardial infarction

Key Points

A new case-control study nested within a large database of human immunodeficiency virus (HIV)-infected patients found abacavir initiation was associated with increased odds of having a myocardial infarction (MI), while longer exposure to abacavir was not.

Additionally, the retrospective study found that the odds of MI increased with increasing cumulative exposure to the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine and stavudine, and most protease inhibitors (PIs), except saquinavir, and particularly to lopinavir with ritonavir and amprenavir/fosamprenavir. No non-nucleoside reverse transcriptase inhibitor (NNRTI) was associated with increased odds of MI.

These results were published in a recent edition of the Archives of Internal Medicine.

They continued on to explain that these conflicting data "have raised a lot of debate because abacavir is 1 of the 2 most-used NRTIs to initiate therapy in the developed world in the recent period." In fact, so much debate has occurred that the authors noted, "the European Medicines Agency asked us whether the ongoing case-control study, nested within the French Hospital Database on HIV (FHDH) Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS CO4), could help settle the issue of abacavir."

CASE-CONTROL STUDY

In order to determine whether exposure to abacavir, other NRTIs, PIs, and/or NNRTIs were associated with increased odds of MI, the researchers designed a case-control study nested within the French Hospital Database on HIV. Within this database, 289 patients who, between January 2000 and December 2006, had a prospectively recorded first definite or probable MI (cases) were identified and randomly matched (up to 5:1 and on age, sex, and clinical center) to 884 HIV patients without an MI history (controls).

Based upon their analysis, researchers unveiled that short-term or recent exposure to abacavir was associated with nearly a 2-fold increased odds of MI (OR, 2.01; 95% CI, 1.11–3.64). This association, however, was attenuated when non-users of cocaine and intravenous drug users were excluded from the analysis (OR, 1.27; 95% CI, 0.64–2.49). Based upon these results, the researchers stressed, "that the relationship between exposure to abacavir and risk of MI cannot be considered causal."

Cumulative exposure to 1 of the 'thymidine analogues' NRTIs, zidovudine or stavudine, was associated with an increased odds of MI (OR, 1.09; 95% CI, 1.00–1.19 per year). No effect was found with other NRTIs including didanosine, lamivudine, tenofovir, or zalcitabine.

Moreover, cumulative exposure to all PIs except saquinavir was associated with increased odds of MI (OR, 1.15; 95% CI, 1.06–1.26 per year). The odds of MI with amprenavir/fosamprenavir (with or without ritonavir) were increased by 53% (OR, 1.53; 95% CI, 1.21–1.94 per year) and odds ratio for lopinavir with ritonavir by 33% (OR, 1.33; 95% CI, 1.09–1.61 per year).

NNRTI use was not associated with elevated odds of having an MI (OR for efavirenz, 1.01 and for nevirapine, 1.00).

At the end of 2006, an estimated 1.1 million persons in the United States were living with HIV infection. As patients infected with HIV continue to live longer lives, cardiovascular disease has become an important cause of morbidity and mortality, with HIV-infected individuals experiencing a 1.5- to 2-fold increase in cardiovascular disease.

SOURCES

Lang S, Mary-Krause M, Cotte L, et al; Clinical Epidemiology Group of the French Hospital Database on HIV. Impact of individual antiretroviral drugs on the risk of MI in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med. 2010;170:1228–1238.

Centers for Disease Control and Prevention. Diagnoses of HIV infection and AIDS in the United States and Dependent Areas, 2008. Available at: http://www.cdc.gov/hiv/surveillance/resources/reports/2008report. Accessed August 10, 2010.

Grinspoon SK, Grunfeld C, Kotler DP, et al. State of the science conference: Initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary. Circulation. 2008;118(2):198–210.