amfAR, The Foundation for AIDS Research

HIV Does Early, Lasting Damage to Immune System

Study finds no association between agitated immune system, HIV levels on ART

For years, researchers have debated whether the tiny amounts of HIV that linger in patients on antiretroviral therapy (ART) influence, or are influenced by, the inflammation that persists even when a person is on ART.

But a recent study in PLOS Pathogens has found that the two are independent of each other. That means inflammation, or immune activation, is not promoting viral replication in the HIV reservoir.

Dr. John MellorsDr. John MellorsInstead, the abnormal immune response stems from damage the virus causes before patients begin treatment, according to the study published April 20.

“The immune system stays activated, angry, upset and inflamed despite current treatments, and that’s not good,” study leader Dr. John Mellors said in an interview with the Pittsburgh Post-Gazette. Mellors is chief of the University of Pittsburgh’s Division of Infectious Diseases.

Inflammation can increase the risk of heart attack, vascular disease, and stroke in HIV-infected patients. In fact, research shows people with HIV are up to twice as likely as people without to have heart attacks even after controlling for factors such as elevated cholesterol, high blood pressure, and smoking.

Previous studies have produced conflicting findings on the link between viral levels and immune activation, possibly because they examined a single point in time without taking into account a patient’s pretreatment status. The current investigation looked at plasma and blood samples taken from 101 participants in the National Institutes of Health-funded AIDS Clinical Trials Group—before ART, one and four years into treatment, and once again between six and 15 years.

"The immune system stays activated, angry, upset and inflamed despite current treatments, and that’s not good"All the participants reached undetectable viral levels a year into treatment and maintained viral suppression for an average of seven years.

According to the authors, while HIV levels were correlated with markers of immune activation in participants before treatment, the association disappeared once they began ART.

“Higher levels of inflammation, T cell activation and cycling [T cell replication] before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression,” they wrote.

The findings suggest that diagnosing HIV early and starting ART as soon as possible may prevent elevated inflammation levels, said lead author Dr. Rajesh Gandhi of the Massachusetts General Hospital Division of Infectious Diseases.

“The results also suggest that new strategies focused on reducing immune activation may need to be added to novel interventions designed to reduce and eventually eliminate HIV,” he said.