Update on Inflammation and Cardiovascular Risk in People With HIV

Cardiovascular Risk and HIV Treatment

The findings from these recently presented studies raise questions about the findings from the DAD study. It will be interesting to see in the months ahead what these and other studies find as they continue their analyses.

Another finding from DAD was that in 2008 it announced that the use of ddI (Videx EC, didanosine) was linked to a nearly 50% increased risk for heart attack. Yet the next year, this apparent risk disappeared. This is very puzzling.

The findings from the French Hospital Database and the Veterans Administration studies are reassuring about the safety of abacavir. They draw attention to previously overlooked CVD risk factors in HIV-positive people, such as chronic kidney disease and the use of cocaine and other illicit substances. However, the results from the FHDB and the VA studies do not negate DAD's results. Rather, they should encourage researchers to try to explore and understand why DAD and a randomized but smaller study of treatment interruption called SMART both found that abacavir was linked to the development of a heart attack.

What's more, compared to DAD, FHDB and the VA, two relatively smaller but randomized studies -- BICOMBO and STEAL -- found conflicting results. And yet another randomized study about the same size as STEAL and BICOMBO, called ARIES, found that abacavir is not associated with heart attacks when used with or without ritonavir (Norvir)-boosted atazanavir (Reyataz). Overall, these conflicting findings and different study designs have led to some confusion among doctors and their patients as they try to make sense of this complexity.

If there is any relatively good news out of this complexity it is this: The proportion of people who have developed a heart attack in databases such as DAD and FHDB is relatively low -- about less than 2%. This should be very reassuring to both doctors and their patients: Heart attacks in HIV-positive people taking HAART are not common.

What to Do?

At the 2009 Conference on Retroviruses and Opportunistic Infections (CROI), Dr. Peter Reiss, a member of the DAD steering committee, suggested that doctors should not prescribe abacavir to patients at high risk for cardiovascular disease. This course of action is prudent. Also, based on the most recent analysis from the French Hospital Database, it seems that doctors may wish to consider not prescribing abacavir for patients who use cocaine or who inject illicit substances.

Additional suggestions may not be forthcoming until researchers can clear up the various results among different datasets and clinical trials and draw robust conclusions.

All of the researchers who participated in the different studies agree when it comes to the following point: Regardless of the anti-HIV treatment being used, an important step would be to greatly reduce or, when possible, eliminate all modifiable risk factors for cardiovascular disease -- and to make the sustained commitment necessary to do so. HIV-positive people who have minimal co-existing complications have the potential to live near-normal life spans thanks to HAART. If this potential is to be realized, the risk factors for heart attacks, stroke and other complications of ageing need to be addressed.

References

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2. Lundgren J, Reiss P, Worm S, et al. Risk of myocardial infarction with exposure to specific ARV from the PI, NNRTI, and NRTI drug classes: The D:A:D study. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal, Canada. Abstract 44LB.
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6. Reiss P. The art of managing human immunodeficiency virus infection: a balancing act. Clinical Infectious Diseases. 2009 Nov 15;49(10):1602-4.
7. D:A:D Study Group, Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008 Apr 26;371(9622):1417-26.