New Med Could Prevent Heart Disease in People With HIV
Call it a PrEP to protect against heart disease in people with HIV.
A large, multi-site clinical trial dubbed REPRIEVE has begun enrolling across the U.S. and around the world to examine whether a medication called pitavastatin can prevent cardiovascular disease in people with HIV.
People with HIV are at a much greater risk for cardiac events than the general population when controlling for other factors such as smoking, high blood pressure and high cholesterol. The trial is looking for people who do not have other risk factors to see if taking pitavastatin daily can prevent cardiovascular problems from happening.
These days, long-term survivors of HIV aren’t dying from opportunistic infections very often thanks to modern antiretroviral therapy, or ART. Instead, cancers and heart disease are the leading causes of death.
Because HIV creates a chronic state of inflammation in the body, the risk of cardiovascular events is high too.
In an interview with HIV Equal, Dr. Steven Grinspoon, a principal investigator for the study from Massachusetts General Hospital/Harvard Medical School, explained how the inflammation occurs.
When HIV infects the body, it targets the lymphoid tissue in the gut, and the tissue becomes depleted. “The gut then becomes leaky and full of bacterial-related cytokines, particularly those called lipopolysaccharides, and that sets off an inflammatory cascade,” Grinspoon said.
Clogged arteries can lead to heart attack
The immune system still performs well overall when ART begins, which is why people with HIV no longer acquire infections like PCP and die from it. “But there is an ongoing inflammatory activation even at the same time that the immune modulation has improved,” Grinspoon explained. “So there is both improvement of immune suppression and ongoing immune activation.”
Even with the most powerful ART medication available, it “may not fully oppress the associated inflammation,” Grinspoon said. “At a low level it’s always there.”
The activated immune cells contribute to a plaque buildup in the arteries, also called atherosclerosis, or “clogged arteries.” Add to that risk that a side effect of ART is higher cholesterol levels, and the risk of cardiovascular disease becomes even higher. It’s precisely why doctors relentlessly warn people with HIV not to smoke, which increases the risk of heart disease even further.
Pitavastatin belongs to a class of medications called statins which are known to both lower cholesterol levels and reduce inflammation. While other statins have been shown to interact poorly with ART, pitavastatin does not, Grinspoon said, because it is processed differently from other statins.
Volunteers still needed for REPRIEVE trial
So far, the trial has enrolled 800 people, but more than 6,500 volunteers are needed. More than 70 of 120 total sites already have been activated. In addition to the U.S., trials will be conducted in Canada, Thailand and Brazil. You can click here to find a list of sites enrolling in the U.S. The study is looking for participants between the ages of 40 and 75 who do not already have a history of cardiovascular disease and who have been on ART for at least six months. They must not be taking a statin already or be on a list of those who are recommended to be given statins.
Grinspoon said the study will examine more than just whether statins are safe and effective in preventing cardiovascular disease in people with HIV. The study also will offer important data about the effect of inflammation on the liver and kidneys as well as whether statins can help lessen the risks of diabetes and cancer in people with HIV.
If the pitavastatin is deemed effective before the trial ends, the trial could be unblinded, and volunteers being given placebo would be given pitavastatin. “There will a very rigorous review by the data safety monitoring board every six months,” Grinspoon said.