While traditional risk factors associated with cardiovascular disease such as smoking, hypertension, cholesterol, and diabetes do affect patients with HIV, these factors only account for about one-quarter of the increased cardiovascular disease risk usually seen in these patients.

Steven K. Grinspoon, MD, Professor of Medicine at Harvard Medical School, noted that the remaining 75% of cardiovascular issues in patients with HIV likely have to do with inflammation linked to excess immune activation, but better algorithms are needed to identify those patients who are most at risk.

A study by Dr Grinspoon and his colleagues that looked at data on more than 100 men with HIV and 41 who did not have HIV concluded that patients with HIV who have excess coronary plaque are often not well identified.2 Another study that examined soft plaque buildup concluded that buildup is more common and extensive in men who have HIV when compared with men who do not have HIV, independent of established cardiovascular disease risk factors. 3

A recently-published review by Mark. J. Siedner, MD, MPH, of Harvard Medical School, Massachusetts General Hospital Center for Global Health, that examined relationships between timing of antiretroviral (ART) initiation and cardiovascular disease (CVD) risk concluded that while there is a “role for ART in mitigating CVD risk at lower CD4 counts … data also suggest that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk.” 4


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People with HIV are 50-70% more vulnerable to heart attack and stroke than people who do not have HIV,5,6 making the need to better identify those patients with HIV and cardiovascular complications, as well as better medications, all the more important, Dr Grinspoon explained.   

A REPRIEVE From HIV and Cardiovascular Disease?

The Randomized Trial  to Prevent Cardiovascular Events in HIV, or REPRIEVE Trial, is a randomized trial seeking to enroll 6500 study participants to test a statin medication called pitavastatin 4 mg (LIVALO, Kowa Pharmaceuticals), explained Dr Grinspoon, who is involved in the trial. 

In addition to the National Institute of Health’s Heart, Lung, and Blood Institute (NIHLBI), the study is funded by the NIH Office of AID Research,  Kowa, and Gilead and supported by the AIDS Clinical Trials Group and the NIH Division of AIDS.

Dr Grinspoon noted that almost 1500 people have been enrolled in the study in more than 80 sites currently running across the United States and internationally. The medication is being given to HIV patients not usually considered at high risk for cardiovascular issues. Dr Grinspoon said that REPRIEVE is “a critical trial to assess how we can predict disease and how well we can prevent it using a newer statin.” Dr Grinspoon said that at full-enrollment, REPRIEVE will be the largest study examining HIV and cardiovascular disease.

In addition to the REPRIEVE Trial, Dr Grinspoon noted other ongoing research consists of imaging procedures to identify plaque with coronary angiography, inflammation identification in patients with HIV, and the Strategies for Management of Anti-Retroviral Therapy (SMART)  and START studies, the last of  which  is examining if early ART will improve cardiovascular risk and events.

As Patients With HIV Live Longer,  Special Challenges Arise

“There are many, many challenges,” Dr Grinspoon said about what an aging HIV population and the physicians who treat them face.

Physicians will have to “work even harder to predict and prevent cardiovascular and other comorbidities,” he added, especially because HIV patients may experience an accelerated aging process. “HIV patients at a younger age often experience the same amount of cardiovascular disease as someone older, so if there is this accelerated pattern it may only get worse as HIV patients get older.”

Chris Longenecker, MD, who runs an HIV cardiometabolic risk clinic as a preventive cardiologist at University Hospitals in Cleveland recently told Infectious Disease Advisor that examining the patient’s total lifestyle is key when evaluating cardiovascular disease or diabetes risk. 

“There are potential variables with co-infected HIV patients and you need to consider diet, daily physical activity and socioeconomics.,” Dr Longenecker explained. 

Disclosure

Dr Grinspoon is a REPRIEVE trial researcher and Kowa Pharmaceuticals provides research funding.

References

  1. Subramanian S, Tawakol A, Burdo TH et al. Arterial inflammation in patients with HIV. JAMA. 2012;308(4):379-386.
  2. Zanni MV, Abbara S, Lo J et al. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS. 2013; 15;27(8):1263-72.
  3. WS Post et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014; DOI: 10.7326/M14-1754.
  4. Siedner MJ. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection. Open Forum Infect Dis. 2016; doi: 10.1093/ofid/ofw032
  5. Triant VA, Lee H, Hadigan C et al. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007;92(7):2506-12.
  6. Freiburg MS, Chang CC, Kuller LH et al. IV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614-22.