Myocardial infarction risk rises with each year of antiretroviral therapy, but remains low

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Each additional year of antiretroviral therapy boosts the risk of myocardial infarction (MI) by 17%, according to an updated report from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study researchers at the 12th Conference on Retroviruses and Opportunistic Infections in Boston, Massachusetts.

Combination therapy remained an independent predictor of MI after statistical adjustment for classic risk factors. Still, the new MI rate remained low—3.6 MIs per 1000 person-years—after 6 years of follow-up of the D:A:D cohort, a distillation of data from 11 European, Australian, and US HIV cohorts.

An earlier published report by the group charted a 26% jump in HIV risk for each year of combination antiretroviral therapy after 36,199 person-years of follow-up. Harlem Hospital’s Wafaa El-Sadr, MD, offered the latest D:A:D analysis, including 76,577 person-years of follow-up on 23,441 people with HIV.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

combination therapy

A therapy composed of several drugs available either as separate tablets, or as fixed-dose combination (FDC).

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

About two thirds of the cohort had taken a protease inhibitor, for a median duration of 1.6 years. One third had been treated with a nonnucleoside reverse transcriptase inhibitor, and 82% with a nucleoside reverse transcriptase inhibitor. Average exposure to any antiretroviral combination was 4.46 years.

High proportions of D:A:D participants have other MI risk factors: 47% smoke, 42% have elevated lipid levels, and 23% have lipodystrophy.

Dr. El-Sadr and colleagues tallied 277 MIs, 79 (28.5%) of which were fatal. Compared with the 18% of cohort members who never took an antiretroviral, those with antiretroviral experience saw their MI rate rise with each passing year of therapy—1.94 times higher with 1 to 2 years of treatment, 3.09 times higher with 3 to 4 years of treatment, and 4.60 times higher with 6 or more years of treatment.

After statisticians accounted for other risk factors, the overall MI risk proved 1.17 times higher per year of combination therapy when compared with no treatment. This heightened risk held true regardless of sex or age.

But antiretroviral therapy was hardly the only variable that increased MI risk. Male sex, previous cardiovascular disease, family history of heart disease, smoking, and every 5 extra years of age all independently raised the MI risk. All of these classic risk factors upped the risk than antiretroviral therapy.

Further study suggested that raised lipids partially but not completely account for the inflated odds of a heart attack. In an analysis adjusted for other risk factors, MI risk rose 12% with each millimole per liter increase of total cholesterol and 12% with every 2-fold jump in triglyceride level.

The D:A:D analysis could not account for every conceivable contributor to heart disease. Researchers did not collect data on insulin resistance, for example. Nor did they know how many heart attack victims may have used cocaine or anabolic steroids. Still, Dr. El-Sadr and colleagues urged clinicians to monitor people with MI risk factors more closely and to work toward reversing remediable risk factors.

D:A:D statisticians have not analysed MI risk according to antiretroviral drug class.

This content licensed to aidsmap by iMedOptions, publishers of http://clinicaloptions.com. Copyright iMedOptions, LLC, 2005

For more coverage of CROI from Clinical Care Options for HIV, including news reports, detailed Capsule Summaries and PowerPoint slides of the key studies, and analysis from our panels of leading experts, visit http://clinicaloptions.com/croi

References

El-Sadr W et al. Relationship between prolonged exposure to combination ART and myocardial infarction: effect of sex, age, and lipid changes. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 42, 2005.

The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 349:1993-2003, 2003.