December 15, 2014
Concerns that HIV-infected individuals are at heightened risk for cardiovascular disease can induce angina. The numbers do not lie: Rates of heart attacks and strokes are higher among the infected compared to the uninfected. Of course, they should be, as more people with HIV smoke than those in the general population. So, the trick to determining if HIV and HIV-related factors are responsible for excess cardiovascular disease risk is to get a great control group to compare infected persons with. (Good luck.)
The closest we have to such a comparator is in the Multicenter AIDS Cohort Study (MACS). This observational study has been following a few MSM in a few U.S. cities for decades. Both HIV-infected and -uninfected men are enrolled, providing an excellent opportunity for comparison of cardiovascular disease and its determinants.
In a cross-sectional study of MACS participants including 618 HIV-infected and 383 HIV-uninfected men without a history of cardiac surgery/intervention and between the ages of 40 to 70 years, CT scans for coronary calcium scoring were performed. In addition, CT angiography was done to assess for plaque characteristics in 450 of the HIV-infected and 309 of the HIV-uninfected participants who had no evidence of chronic renal insufficiency.
Remarkably, plaque was ubiquitous in both infected and uninfected men: 78% and 74%, respectively. After full adjustment for major confounders, there remained a higher prevalence of plaque in those who were HIV infected -- although after adjusting for age, race, CT scanning center, cohort and CAD risk factors, the association between HIV and presence of coronary calcium became only "borderline significant."
Importantly, HIV-infected men were also more likely to have noncalcified plaques (the most vulnerable to rupture). Older age was associated with noncalcified plaque in the HIV-infected but not HIV-uninfected men, and this seemed to drive the overall differences between these groups. Actual coronary stenosis was seen in 17% of HIV positives and 15% of HIV negatives, and no significant differences were found after adjustment.
This study is fascinating on many levels. It is among the best at comparing HIV-infected and -uninfected persons using rigorous and objective evaluations. The persistence, if not increase, in noncalcified plaque in older HIV-infected men stands out. While plaque starts to calcify in the uninfected, it remains soft and vulnerable in those with HIV. Why this is remains unclear.
Also interesting is that despite the nature of the cohort and the homogeneity one would expect to see regardless of HIV status, there remain differences between the HIV-infected and -uninfected MACS participants, including demographic characteristics, lipids, BMI and current smoking status. Increasing adjustment for these -- as well as other traditional risks for cardiovascular disease -- appeared to attenuate the strength of some of the findings. With consideration of additional unmeasured factors, the associations could become even weaker. To be fair, this will always limit studies comparing HIV-infected persons to a control group, but it does make it difficult to tag blame for differences solely on the virus, antiretroviral therapy or other HIV-related factors.
The study is an important step toward better understanding of how HIV-infected people are different. Further analyses, including a look at inflammatory markers and perhaps follow-up scanning, are anticipated.
What are some other top clinical developments of 2014? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.
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