Not so long ago, living longer was its own reward for people with HIV. Antiretroviral therapy extended lives, gave hope, and silenced what for many had felt like a ticking clock.
But for the 1.2 million HIV-positive people in the United States, an extended life has come with its own heart aches. Literally.
HIV, or human immunodeficiency virus, doubles a person’s risk of heart disease and triples the chance of a heart attack in women. Fifteen percent of deaths among people living with HIV are related to heart disease.
Recently, in an effort to find ways to turn the tide, the National Institutes of Health (NIH) launched the Randomized Trial to Prevent Vascular Events in HIV, or REPRIEVE. The idea: to test whether a statin, a medication commonly used to lower blood cholesterol levels, can lower the risk of heart disease among people with HIV. Funded by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), REPRIEVE is the largest clinical trial to date focused on HIV-related cardiovascular disease.
“The results from REPRIEVE will provide new information about inflammation and cardiovascular risk in patients with HIV and is an opportunity for scientists in cardiovascular health and infectious diseases to join forces, share resources, and have a meaningful impact on public health,” said Gary Gibbons, M.D., director of NHLBI.
By focusing on heart disease and HIV, REPRIEVE combines two aspects of research that experts say warrant more attention. It also examines the disproportionate impact of these diseases on women. In the United States, around one in four people living with HIV are women, and African American and Hispanic women continue to be disproportionally affected by HIV, according to the Centers for Disease Control and Prevention (CDC). Even when they are receiving treatment, women living with HIV are three times more likely to develop heart disease than their counterparts without the virus.
“There may be unique risk factors for the development of cardiovascular disease in women with HIV and in African-American individuals with HIV,” said REPRIEVE investigator Markella Zanni, MD, professor at Massachusetts General Hospital. “And current guidelines may only take into account a fraction of the risk factors at play in these populations.”
A unique feature of REPRIEVE will be the study of sex differences in the onset, severity and course of HIV and heart disease, as well as in individual responses to the statin treatment.
It will assess “whether immune activation and inflammation contribute uniquely to heart disease risk among women aging with HIV and how statin therapy may reduce heart disease risk,” said REPRIEVE’s investigator Sara Looby, MSN, PhD, professor at Massachusetts General Hospital.
It also will study how sex-specific factors, including levels of women’s sex hormones, contribute to heart disease risk and risk reduction in HIV.
REPRIEVE’s reach will be global in scope. The studies will be carried out at more than 120 sites throughout the United States, Canada, Thailand, South Africa and Brazil. REPRIEVE plans to enroll 6,500 HIV-positive individuals aged 40 to 75, and aims to enroll a percentage of women representative of the prevalence of HIV in each country. In the U.S. about 22 percent of participants will be women, since they represent about one in four of those living with HIV.
Today, HIV affects 35 to 40 million people worldwide, and half are women. “As women have been in the past underrepresented in HIV research and in heart disease research, robust participation of women in REPRIEVE is considered to be essential to the success of the trial,” said Looby. Developing best practices for recruiting and retaining women in clinical trials, she added, will be another contribution to a future of more inclusive research designs.
While continuing with their antiretroviral therapy, the participants will receive either a daily dose of a statin or a placebo to test whether it lowers the risk of heart disease. The statin, Pitavastatin, was chosen because it does not interfere with the antiretroviral therapy (ART) that people living with HIV need to help their bodies control the virus and stay healthy.
The researchers will follow the participants for up to six years, assessing them for the development of cardiovascular events such as heart attacks and strokes.