New technology provides hope for HIV cure strategies

2023

Challenge

In 2021, there were 38.4 million people living with HIV globally. While lifelong antiretroviral therapy allows those infected with HIV to control the virus and live healthy, active lives, in some people, HIV can lie dormant in a small number of infected immune cells for decades, even with continuing antiretroviral therapy. If the therapy is stopped, the virus in these infected cells, known as ‘latent’ HIV, can resume replicating, leading to high numbers of infected cells and, ultimately, to AIDS. For the past 25 years, the persistence of this small population of infected cells has been recognized as a major barrier to curing HIV. Isolating and characterizing those cells in their natural state is necessary for developing a curative therapy, but the technology to do this analysis has long been out of reach.

Advance

IRP researchers led by Eli A. Boritz, M.D., Ph.D., and their collaborators at the University of California, San Francisco, developed a new technology called Focused Interrogation of Cells by Nucleic Acid Detection and Sequencing (FIND-Seq) to measure the activity of genes in cells containing latent HIV. Using data produced by FIND-Seq, the scientists compared the gene activity patterns of HIV-infected memory CD4+ T cells to those of HIV-uninfected memory CD4+ T cells in the same individuals. This led to the discovery of gene activity patterns in infected cells that were associated with the silencing of HIV genes.

Impact

The IRP study provided the first evidence that latent HIV in people receiving antiretroviral therapy arises in part from unique patterns of gene activity in infected cells. These distinctive features help explain the remarkable ability of the virus to persist in the body even when it is not able to spread between cells. An improved understanding of how HIV-infected cells persist in people who are receiving antiretroviral therapy may pave the way to the creation of medications that specifically target those cells in order to completely eliminate HIV from the body.

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