Patients Treated for HIV Still Experience Chronic Inflammation

Researchers at George Washington University have discovered by people living with HIV still experience comorbidities despite successful viral suppression with antiretrovirals. They found that immunological memory persists despite low viral loads and can cause chronic inflammation that leaves patients at risk for certain cardiovascular and neurocognitive conditions.

According to the study, which was published recently in Cell Reports, the HIV protein permanently alters immune cells in a way that causes them to overreact to other pathogens. When the protein is introduced to immune cells, genes in those cells associated with inflammation become expressed, and remain expressed, even when the HIV protein is no longer in the cells. 

Unfortunately, the findings suggest suppression or even eradication of HIV in the body may not resolve this chronic inflammation. “This research highlights the importance of physicians and patients recognizing that suppressing or even eliminating HIV does not eliminate the risk of these dangerous comorbidities,” says Michael Bukrinsky, professor of microbiology, immunology, and tropical medicine at George Washington University’s School of Medicine and Health Science and lead author on the study. “Patients and their doctors should still discuss ways to reduce inflammation and researchers should continue pursuing potential therapeutic targets that can reduce inflammation and co-morbidities in HIV-infected patients.”

The team isolated human immune cells in vitro and exposed them to the HIV protein Nef. The amount of Nef introduced to the cells is similar to the amount found in about half of HIV-infected people taking antiretrovirals whose HIV load is undetectable. After a period of time, the researchers introduced a bacterial toxin to generate an immune response from the Nef-exposed cells. Compared to cells that were not exposed to the HIV protein, the Nef-exposed cells produced an elevated level of inflammatory proteins called cytokines. When the team compared the genes of the Nef-exposed cells with the genes of the cells not exposed to Nef, they identified pro-inflammatory genes that were in a ready-to-be-expressed status as a result of the Nef exposure.

According to Bukrinsky, the findings in this study could help explain why certain comorbidities persist following other viral infections, including COVID-19. “We’ve seen this pro-inflammatory immunologic memory reported with other pathogenic agents and often referred to as ‘trained immunity,’” Bukrinsky says. “While this ‘trained immunity’ evolved as a beneficial immune process to protect against new infections, in certain cases it may lead to pathological outcomes. The ultimate effect depends on the length of this memory, and extended memory may underlie long-lived inflammatory conditions like we see in HIV infection or long COVID.”