https://www.ajmc.com/newsroom/researchers-say-they-can-now-accurately-measure-hiv-reservoirs
Researchers Say They Can Now Accurately Measure HIV Reservoirs

Jaime Rosenberg

Using a new genetic technique, researchers say they can now quickly and accurately identify hidden, inactive pockets of HIV—known as HIV reservoirs—in patients’ cells. This form of HIV embeds into genomes of cells and persists despite otherwise successful therapies, including antiretroviral therapy. As a result, researchers are not able to cure the infection.

Typical treatment for HIV includes regimens of multiple antiretrovirals, with each antiretroviral inhibiting a specific stage of the HIV lifecycle. Because these antiretrovirals are given simultaneously and block 2 or more stages of the HIV lifecycle, the HIV virus cannot replicate, lowering its presence in the bloodstream to levels below detection, thus resulting in viral suppression.

While viral suppression can keep patients healthy for years, the virus still lurks in the body in a latent form that is difficult to detect and count. Researchers have focused on being able to “awaken” and destroy these reservoirs of HIV, known as the shock and kill approach. However, efforts to date have been unsuccessful. In order for this approach to be successful, researchers need to be able to accurately measure how big a patient’s reservoir is so they can track their progress.

Previous tools have likely overestimated the amount of this HIV form by 10- to 100-fold, potentially obscuring meaningful declines in infection from treatment, according to the researchers. Most tools use a technique that relies on a genetic reaction known as polymerase chain reaction (PCR) to measure how much viral DNA is present in the CD4 cells. However, according to Robert Siliciano, MD, PhD, a professor of medicine at the Johns Hopkins University School of medicine and investigator at Howard Hughes Medical Institute, “98% of the HIV instruction books are so defective they’re harmless, so the method overestimates the number that matters to patient health.”

Siliciano and colleagues designed a PCR that distinguishes between defective and intact viral templates by using fluorescent probes in 2 different colors, which target areas prone to mutations that can cause defects. Then, a color read-out indicates whether the HIV DNA are defective or not.

According to the researchers, the new technique can be used to determine whether a treatment is affecting reservoirs of HIV likely to activate and replicate.

“We may still be a long way from a cure, but now at least we can measure our progress,” said Siliciano in a statement.
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