SUMMARY: HIV positive people are at higher risk for cardiovascular disease overall, compared with HIV negative individuals, according to findings from Kaiser Permanente presented this month at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Other studies found that HIV positive people on ART with well-preserved immune function were not at greater risk, however, and that abacavir (Ziagen) was not linked to heart attacks.

By Paul Dalton

As HIV treatment proves increasingly effective, at least in developed countries, attention has shifted to the long-term consequences of both HIV disease and its treatment.

The impact of HIV and antiretroviral therapy on cardiovascular health is of particular interest, as heart disease remains the biggest health issue in the U.S. This year's CROI featured several presentations covering cardiovascular disease and HIV.

HIV and MI Risk

Evidence from the SMART treatment interruption study and elsewhere indicate that HIV infection may lead to an increased risk of myocardial infarction (MI), or heart attack. Two oral presentations at CROI dealt with this topic.

Matthew Freiberg from the University of Pittsburgh (abstract 809) presented an analysis of acute MI risk in the Veterans Aging Cohort Study. This study compared over 27,000 people with HIV to a matched group over 55,000 HIV negative veterans, followed from 2003 through 2008. The cohort is largely male and the average age was 49 years. Overall, the HIV negative veterans appeared to be at increased risk of MI due to some traditional risk factors, particularly diabetes and hypertension.

Results

	People with HIV had a 1.94-fold higher risk of having an acute MI during follow-up.
	The risk of MI from HIV was similar to that of diabetes and smoking in this study.
	Among people who never smoked, HIV was still associated with increased Mi risk.
	HIV positive and HIV negative people had MIs at the same average age, 53 years.
	After adjusting for other factors, class of antiretroviral drugs and CD4 cell count were not associated with MI risk.

These studies suggest that HIV infection increases a person's risk of cardiovascular disease including MI. But there is some evidence that effective treatment of HIV may reduce that risk. There is also evidence that advanced HIV disease contributes to a person's risk of MI.

Abacavir and MI Risk

Abacavir (Ziagen, also in the Epzicom and Trizivir combination pills) is a widely used component of first line antiretroviral treatment. In 2008, an analysis of the D:A:D cohort found that abacavir was associated with an increased risk of MI.

Results from other studies, however, have proved conflicting. For example, GlaxoSmithKline, abacavir's manufacturer, performed an analysis of 54 studies in which abacavir was used and found no increased risk of MI. An analysis of the SMART study, in contrast, found a 4-fold increased risk of MI among those taking abacavir.

In a poster presentation at this year's CROI, Xiao Ding of the U.S. Food and Drug Administration (abstract 808) presented a meta-analysis of 26 randomized controlled clinical trials (RCTs) in which abacavir was used. The analysis included almost 5000 participants, approximately 75% of the men. The researchers divided the studies into those sponsored by the manufacturer, the National Institutes of Health (NIH), and academic institutions.

Results

	There was no statistically significant difference in MI rates between abacavir and non-abacavir trial arms.
	The overall hazard ratio in the pooled studies was 1.02, not a significant difference.
	Manufacturer and NIH studies both saw no increased risk; manufacturer's studies showed a hazard ratio of 0.70 while NIH studies showed 1.06.
	Academic studies showed a hazard ratio of 1.6, but this was not considered statistically significant.

The results from this analysis are likely to fuel the ongoing controversy about abacavir and risk of MI. The controversy includes the classification of abacavir-containing regimens in the DHHS federal HIV treatment guidelines. The current guidelines classify regimens containing tenofovir/emtricitabine (Truvada) as "preferred" and those containing abacavir as "alternative." Abacavir was downgraded based in part on the D:A:D and SMART MI findings.

Investigator affiliations:

3/18/11

References

M Freiberg, K McGinnis, A Butt, et al. HIV is associated with clinically confirmed myocardial infarction after adjustment for smoking and other risk factors. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 809.

M Goetz, S Brown, KA Oursler, et al. Contribution of immunodeficiency to CHD: Cohort study of HIV+ and HIV- Kaiser Permanente members. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 810.

X Ding, E Andraca-Carrera, C Cooper, et al. No association of myocardial infarction with ABC use: an FDA meta-analysis. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 808.