July 23, 2010 - At the same time that medical science has nearly eliminated AIDS deaths in patients treated for human immunodeficiency virus (HIV), two international meetings of HIV/AIDS scientists and patient advocates find major shortcomings in the design and analysis of studies used to assess cardiovascular disease (CVD) risk in people with HIV with significant implications for improving medical care.
Among the deficiencies cited are inconsistent standards for data analyses, lack of transparency in publishing research findings and often conflicting data about the nature and extent of increased CVD risk in HIV patients.
The meetings, convened in Washington and Vienna by the Forum for Collaborative HIV Research, produced an in-depth assessment of the state of research on CVD risk in the HIV population and offered an action plan for improving how studies assessing CVD risk are conducted, analyzed and published. After reviewing current findings from numerous published and unpublished analyses, the more than 100 scientists, clinicians, regulatory officials and members of the HIV patient community attending these sessions agreed that until more is known about the link between HIV and cardiovascular disease, clinicians should consider every HIV patient at increased risk for heart disease. This is because infection with HIV is associated with the onset of heart disease at an earlier age and with deaths that appear to be increasing at an alarming rate.
Coming at a critical time in advancing the HIV/AIDS research agenda, the meetings also focused increased attention on the extent to which chronic HIV disease itself is a risk factor for heart disease. The emerging consensus is that in well-treated patients with HIV, there appears to be an approximate two-fold increase in the risk for heart disease that is specifically related to the virus and/or to drug treatment. Moreover, the risk for heart attack is 70 to 80 percent higher among people with HIV, although the absolute risk still remains low for younger patients.
“Five years ago, there was still debate within the scientific community about whether there is an increased risk for cardiovascular disease. We have the answer to that question. There is an increased risk,” said Veronica Miller, M.D., executive director of the forum. “What is now essential is to learn why, so treatment can be individualized to each patient and based on sound science. To do this, standards for data analysis and transparency must be more stringent.”
Echoing this need, meeting participants addressed the realities for today’s physicians, who often base their treatment decisions on interpreting studies where the methods were not fully published or the sources were not available for peer or independent review. Accordingly, the panel recommended upgrading the standards for data analysis and publication as an immediate research priority so the conclusions of scientific studies will be reliable, relevant to treatment of patients and not based on unfounded science.
As stated by Ralph D’Agostino, M.D., of the Framingham Study, “Conclusions drawn from studies of large populations, like Framingham, must be confirmed before we can recommend that clinical practices should change.”
Focusing on Risk Factors
Focusing on risks that are specific to HIV itself, the meetings discussed the state of the science, which points to continuous high levels of inflammation throughout the bodies of HIV patients – a problem shared with patients affected by other chronic inflammatory diseases, such as lupus. Even though this persistent inflammatory response may not be apparent to the HIV patient or the physician or be detected through routine tests, scientists link the resulting chronic inflammation with damage to the blood vessel endothelium over time, resulting in atherosclerosis – a type of coronary artery disease involving the buildup of plaque in and on artery walls.
Along with chronic inflammation, Forum members focused on metabolic syndrome, a constellation of symptoms including abdominal obesity, high triglyceride levels, low HDL (good) cholesterol, insulin resistance and hypertension – all of which are associated with heart disease. Noting that metabolic syndrome takes on unique characteristics in HIV patients and can be exacerbated by certain HIV drugs, the panel members advocated for evaluating even young HIV patients for metabolic syndrome and taking an aggressive approach when managing lipid abnormalities. The panel also saw the need for more studies on metabolic syndrome, especially to determine the prevalence and incidence of high total, lowered HDL and increased LDL (bad) cholesterol, and high triglyceride levels – abnormalities linked to HIV.
Assessing Known Risk Factors
At the same time, forum members agreed more attention must be paid to assessing and treating known risk factors for heart disease in HIV patients and outlined some immediate steps to make CVD risk assessment a routine part of HIV patient care. Specifically, panel members called on clinicians to evaluate every HIV patient for insulin resistance, diabetes, kidney abnormalities and other abnormalities that might be influenced by HIV or the drug regimen.
“For now, every HIV patient should be considered at risk for cardiovascular disease,” said Jur Strobos, M.D., deputy director of the forum. “We must focus on controlling traditional risk factors, such as smoking, excess weight, hypertension, diabetes, illicit drug use and high blood cholesterol levels. Of key concern is reducing the high prevalence of smoking in people with HIV, which some studies estimate is as high as 50 percent in the HIV patient population.”
The forum convened the series of recent scientific workshops on CVD risk in HIV patients to lay the groundwork for defining the research agenda for the future, especially in light of the deficiencies in existing data from clinical trials and observational studies that have produced conflicting and sometimes controversial findings about HIV disease as an underlying risk for cardiovascular disease. Among the research priorities identified are new studies on concomitant inflammatory and immune activation, their measurement and their potential treatment.
The companion meetings, taking place June 23 in Washington, D.C., and as a symposium held at the International AIDS Society meeting July 18 in Vienna, brought together infectious disease experts, cardiologists, endocrinologists, specialists from the statistical community and regulatory representatives from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). As a follow-up to these meetings, the Forum will publish a summary report later in the year providing new recommendations for research studies and new metrics.
Forum for Collaborative HIV Research
Now part of the University of California (UC), Berkeley School of Public Health and based in Washington, D.C., the Forum was founded in 1997 as the outgrowth of the Keystone Center's report “The Keystone National Policy Dialogue on Establishment of Studies to Optimize Medical Management of HIV Infection” (www.hivforum.org/storage/hivforum/documents/keystone_document.pdf), which called for an ongoing collaboration among stakeholders to address emerging issues in HIV/AIDS and set the research strategy.
Representing government, industry, patient advocates, healthcare providers, foundations and academia, the Forum is a public/private partnership that is guided by an Executive Committee that sets the research agenda. The Forum organizes roundtables and issues reports on a range of global HIV/AIDS issues, including treatment-related toxicities, immune-based therapies, health services research, co-infections, prevention, and the transference of research results into care. Forum recommendations have changed the ways that clinical trials are conducted, accelerated the delivery of new classes of drugs, heightened awareness of TB/HIV co-infection, and helped to spur national momentum toward universal testing for HIV.
For more information: www.hivforum.org