Researchers have long understood that chronic inflammation is a health concern for people with HIV, even those with an undetectable viral load. This has led some to speculate that even tiny amounts of virus in the blood might be kicking the body's immune system into perpetual overdrive, eventually putting even well-controlled HIV patients at greater risk of cancer, heart disease, kidney disease and other health problems.
Some doctors have proposed adding a fourth drug to traditional antiretroviral therapy regimens as a way to further diminish viral load, potentially reducing inflammation. But groundbreaking new research indicates that inflammation won't be so easy to tackle. A new study published in PLOS Pathogens revealed that a person's viral load prior to starting antiretroviral therapy directly determines his or her level of inflammation later in life.
"We found that inflammation and viral load do correlate before patients start on therapy," said the study's lead author, Rajesh T. Gandhi, M.D., Massachusetts General Hospital Infectious Diseases Division and Ragon Institute. However, he added, "once on therapy, the tiny amount of virus in the blood did not correlate with inflammation. Instead, the people with the most inflammation before starting therapy had more inflammation while on therapy."
In other words, HIV-positive people who delayed starting treatment were more likely to develop a higher viral load, and therefore more likely to suffer from chronic inflammation even after getting the virus under control.
Gandhi's research provides new evidence to support the idea that getting tested and treated soon after exposure can dramatically improve a person's health, even decades later. In addition, he hopes his results will spur research into other promising methods of reducing inflammation, such as adding anti-inflammatory medication rather than intensifying antiretroviral therapy.
"Our results show that more [antiretroviral therapy] is not the answer," Gandhi said. "Adding a fourth drug is probably not going to reduce inflammation. Once you're on therapy, the virus is in check."
The study relied on blood samples taken from patients who were members of the AIDS Clinical Trial Group. This group was unique in that study participants were asked to give a blood sample prior to starting on antiretrovirals, and then stayed in touch with the study coordinators and continued to give blood samples in the years after they started treatment.
Gandhi used an ultra sensitive piece of equipment that can detect miniscule amounts of HIV virus in the blood -- far beyond what traditional laboratory tests can detect. By comparing the pre- and post-therapy viral levels and inflammatory markers in 101 patients, Gandhi's team was able to draw a clear line between pre-antiretroviral therapy viral load and inflammation levels post treatment.
Despite the fact that all the participants on antiretrovirals had suppressed plasma RNA levels to less than 50 copies/mL, those with higher plasma RNA levels prior to treatment continued to have more inflammation, even in blood tests conducted four and six years after starting treatment.
"I was struck by the fact that even after a decade of [antiretroviral] treatment, inflammation levels stayed high," said Gandhi. "That is not what I thought was going to happen. I did not think that their pre-therapy values would have a such an influence in the years to come."
According to Gandhi, this research is groundbreaking because previous data on the link between viral load and inflammation has been conflicting.
"While there have been have been studies linking inflammation and viral level, the weakness in those studies is that most were very small and did not have the advantage of measuring pre-therapy blood levels," he said. This research clears the air about the connection between viral load and inflammation, and also informs scientists' understanding of the viral reservoir.
This research demonstrates that, counter to prior assumptions, the viral reservoir is not being driven, or "re-lit," by inflammation. "That is an important understanding about the viral reservoir that was uncertain before," Gandhi said.