Human immunodeficiency virus (HIV) works by entering specific immune cells and replicating inside them. People with HIV are treated with antiretroviral therapy (ART), which prevents viral replication, but some individuals taking ART continue to have low levels of viral presence in the bloodstream, or viremia. This condition is usually attributed to drug resistance or ineffectiveness of ART, but recent studies have found that low-level viremia can occur even without these driving forces, a condition known as non-suppressible HIV viremia (NSV).
A team led by researchers at the Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, recruited eight participants with NSV despite receiving ART and analyzed both the virus and host immune response.
Using sequencing assays, the researchers found large reservoirs of proviruses — viral genetic material that has been integrated into host DNA — inserted into transcriptionally active regions of immune cell genomes. 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 led to dampened immune responses and increased survival of cells infected with HIV.
The authors also suggest that these mechanisms could contribute to low levels of residual viremia in most individuals with HIV, even if they successfully undergo ART.
“Our study has identified potential mediators of non-suppressible viremia,” said Jonathan Li, MD, of the Division of Infectious Diseases. “Furthering our understanding of these mechanisms could help develop strategies to disrupt viral persistence in all patients living with HIV.”
Read more in Nature Medicine.
Method of Research
Subject of Research
Human tissue samples
Viral and host mediators of non-suppressible HIV-1 viremia
Article Publication Date
J.R.C.M. has received funding from Gilead Sciences for investigator-initiated research paid to his institution. P.L.A. has received past consulting fees from Gilead, ViiV and Merck and research funding from Gilead paid to institution, unrelated to this work. G.D.G. has received grant funding from Merck. J.Z.L. has consulted for Abbvie and received grant funding from Merck. The other authors declare no competing interests.