Mining the Blood for Markers of the Reservoir
By Jeffrey Laurence, M.D., and Rowena Johnston, Ph.D.
Most people living with HIV (PWH) must take daily antiretroviral therapy (ART) to control the virus, but a rare few known as viremic controllers (VCs) can maintain fairly low viral loads in the absence of ART, and an even smaller number known as elite controllers (ECs) maintain undetectable virus levels without ART. In all cases, a reservoir of mostly inactive virus, largely in tissues that are difficult to access, is the main barrier to an HIV cure.
Antibodies, the most exquisitely sensitive detectors of virus that we have, may hold the key to understanding how ART-free control of HIV can be achieved. And they may even provide an easy-access method to help us understand the size and behavior of the reservoir hidden in inaccessible tissues throughout the body.
Sixty-four PWH, including 12 ECs, 23 VCs, 17 with undetectable virus on ART, and 12 with detectable virus and no treatment, were studied, along with HIV-negative control subjects. A total of 293 HIV antibody characteristics—such as their quantity, the region of the virus they target, and the antiviral functions they trigger—were tested in the blood of all subjects. These were compared with viral load, and with proviral DNA, as a measure of the size of the HIV reservoir.
Results were analyzed utilizing a machine learning technique that trains a computer to detect patterns in large amounts of data. Unanticipated correlations were found, such as an association of antibody levels against an “accessory” HIV protein, Vif, with reservoir size.
The authors concluded that “the development of these tools may represent simple biomarkers for the rapid evaluation of changes in viral replication outside of the blood and changes in the reservoir size.”
amfAR was a funder of this research.
Dr. Laurence is amfAR’s senior scientific consultant and Dr. Johnston is vice president and director of research.