Epidemic of cardiovascular disease in HIV patients `not on horizon`

An epidemic of cardiovascular disease in HIV-positive people receiving protease inhibitor-based treatment is not on the horizon, according to an editorial in the April 27^th edition of the New England Journal of Medicine. Commenting on the findings of the DAD study, also published last week, James Stein of the University of Wisconsin School of Medicine says HIV infection uncontrolled by treatment is likely to be a greater risk for heart disease than the metabolic changes associated with HIV treatment.

The DAD study (Data Collection on Adverse Events of Anti-HIV Drugs) collected data on adverse events in 23,347 HIV-positive patients in Europe, Australia and North America receiving antiretroviral therapy for up to six years, beginning in 1999. Findings were first presented in the New England Journal of Medicine in 2003 and subsequently at the Twelfth Conference on Retroviruses and Opportunistic Infections in 2005.

The full findings on the risk of myocardial infarction (heart attack) were reported in the April 27^th edition of the New England Journal of Medicine, and show that individuals treated with protease inhibitors had a 16% increased risk of heart attack for each year of protease inhibitor exposure. This risk declined to 10% per year after adjusting for the effect of lipid elevations (relative risk 1.10, 95% confidence interval 1.04 – 1.18). The increase in risk for people exposed to non-nucleoside reverse transcriptase inhibitors was not statistically significant.

The study currently lacks sufficient follow-up to detect differences in the risk of cardiovascular disease between drugs in the protease inhibitor class.

The authors of the DAD study note that their finding of an association between protease inhibitor treatment and cardiovascular risk corresponds to a 50% increase in risk after five years of treatment.

“The magnitude of this association is similar to the increment in risk attributable to diabetes or cigarette smoking and is greater than that associated with a family history of cardiovascular disease. Whether this effect translates into an important additional absolute risk depends on his or her preexisting cardiovascular disease risk profile.”

However, in his accompanying editorial Dr James Stein, Associate Professor in the Division of Cardiovascular Medicine at the University of Wisconsin School of Medicine and director of the university hospital’s preventive cardiology programme, says that the magnitude of increased risk per year [editor’s italics] is not high compared to the risk of current smoking in the DAD study (relative risk 2.83) or male sex (1.91).

Also, “the incidence of myocardial infarction among patients exposed to protease inhibitors for more than six years was only 0.6% per year,” he writes. “This risk of cardiovascular disease would be considered low or at most moderate, depending on a patient’s risk factor burden. Thus there does not seem to be an epidemic on the horizon – simply a risk that needs to be managed.”

“Given the much greater cardiovascular risks associated with diabetes mellitus and with smoking (and the high prevalence of smoking among HIV-infected patients), perhaps more effort should be spent assisting our patients with smoking cessation and the prevention of diabetes, rather than our focusing so intently on the dyslipidemic effects of antiretroviral therapy.”

He notes that in the SMART study of HIV treatment interruption, individuals who interrupted treatment had a 60% higher risk of cardiovascular disease during a 16 month follow-up period, “indicating that effective viral suppression actually may reduce short-term cardiovascular risk.”