The Past, Present, and Future of HIV Reservoir Cells

Research Question

The HIV reservoir consists of HIV-infected cells that are difficult to characterize because to date they have been indistinguishable from uninfected cells. Once the HIV inside infected cells is activated, many of the surface and interior characteristics change. While activated reservoir cells are easier to identify and isolate from blood samples, these fundamental changes mean they are no longer typical reservoir cells. Thus the challenge for researchers is to work out what an activated infected cell in the present looked like in the past.

Findings

Researchers from the amfAR Institute for HIV Cure Research, led by Dr. Nadia Roan, combined two technologies. First, they characterized levels of 39 surface and intracellular proteins of activated CD4 T cells in the blood, lymph nodes, and gut of eight individuals on long-term antiretroviral therapy. Next, they used a method previously developed at the Institute to back-calculate the combination of proteins the cells likely possessed immediately prior to stimulation. Using these tools, the researchers discovered a group of eight to ten proteins that, when considered in combination, reliably identified resting HIV reservoir cells.

Impact

The ability to accurately identify true resting reservoir cells will enable researchers to isolate them from the blood and tissues of people living with HIV so that the effects of curative interventions can be studied more closely. It will also enable doctors to quantify how much reservoir remains after a clinical intervention and will help determine if the person is cured of HIV.

amfAR’s Role

amfAR was a funder of this research.

Original Article

https://pubmed.ncbi.nlm.nih.gov/32990219/

Dr. Johnston is an amfAR vice president and director of research.

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