Human immunodeficiency virus (HIV) works by entering certain immune cells and replicating inside them. People with HIV are treated with antiretroviral therapy (ART), which prevents viral replication, but some people who take ART have a low viral presence, or viremia, in their bloodstream. This condition is usually attributed to drug resistance or ineffectiveness of ART, but recent studies have shown that low-level viremia can occur without these driving forces, known as non-suppressible HIV viremia (NSV).
A team led by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham Health Care System, recruited eight participants with NSV despite receiving ART and analyzed both the virus and the host immune response.
Using sequencing assays, researchers have found large reservoirs of proviruses -; Viral genetic material that has integrated into host DNA -; inserted into transcriptionally active regions of the immune cell genome. Although unable to replicate due to ART, these proviruses contained mutations that helped them evade detection and were able to express genes leading to the NSV phenotype. In addition, the investigators found that the study participants had altered gene expression patterns that reduced the immune system’s ability to survive HIV-infected cells.
The authors also suggest that these mechanisms may contribute to the low level of residual viremia in most people with HIV, even if they are successfully on ART.
Our study identified potential mediators of non-suppressible viremia. Our further understanding of these mechanisms may help develop strategies to disrupt viral persistence in all patients living with HIV.”
Jonathan Lee, MD, Department of Infectious Diseases