Lead


Lay summary
Ever since the availability of highly active combinations of anti-HIV medications (antiretroviral therapy or ART) in 1995, HIV-infected individuals have a dramatically improved quality of life and prolonged life expectancy. However, new health concerns have emerged in HIV-infected persons, including an increased risk of so-called "metabolic" complications, which include cholesterol problems, high blood pressure, diabetes and, most concerning, an increased risk of heart attack at a premature age. This increased heart attack risk has been attributed to a number of factors, including the fact that HIV-infected persons smoke more, and certain ART medications which increase the heart attack risk by increasing the level of "bad" cholesterol and other mechanisms. In addition, it has long been known that the risk of having a heart attack is approx. 50% hereditary, i.e. a genetic predisposition may explain 50% of the risk. However, the genes that are involved in this predisposition were not well known until 2007. That year, a number of large studies that have scanned the entire DNA (genome) of thousands of people without HIV infection (so-called genome-wide association studies) have established an inventory of >50 gene variants that are reliably linked to heart attack risk. The aim of our study is to look at these gene variants (so-called single nucleotide polymorphisms or SNPs) in HIV-infected individuals, in order to see if we can find a set of SNPs that can predict heart attack risk. We will study 2400 HIV-infected patients. Of these, 600 have had heart attacks (or heart vessel dilation and stenting or heart bypass surgery) and 1800 "control" patients who have not. To this end, an international consortium of 17 collections of HIV-infected persons (cohort studies) from Europe, the US, and Australia, has been established, the lead being taken by the Swiss HIV Cohort Study (www.shcs.ch). We will assess to what extent SNPs and known "risk factors", including smoking, cholesterol levels, etc. explain the risk of having a heart attack in these patients. Identifying a genetic predisposition to heart attack in HIV-infected patients would represent an important scientific advance. It would not only enhance our scientific understanding of the factors that lead to heart attacks, but would have important implications for the medical care of HIV-infected persons: In persons at high genetic risk of heart attack, the HIV specialist might select a different (more heart-friendly) ART combination of drugs, or might make increased efforts at getting the patient to quit smoking, at treating high blood pressure etc.