December 11, 2019

While no true cure for HIV/AIDS exists, patients can suppress the virus through a continuous regimen of medication. But now, scientists have discovered a new approach to dealing with HIV infection—one which could eliminate the need for such ongoing treatment.

The study was conducted at the Wisconsin National Primate Research Center (WiNPRC) with the University of Miami (UM) Miller School research team, the Frederick National Laboratory for Cancer Research in Maryland and the Gene Therapy Center at the University of Massachusetts Medical School.

In the study, researchers used an adeno-associated virus (AAV) to deliver gene products into the muscle cells of nonhuman primates, turning the cells into “factories” which produce genetically engineered antibodies indefinitely.

One primate in the study had an exceptionally positive response to the new approach. After receiving a single injection of the AAV-delivered antibodies, its HIV viral load immediately dropped below the limit of detection and has remained undetectable for more than three years.

According to Ronald C. Desrosiers, PhD, professor of pathology at UM and a longtime HIV researcher, this result provides proof of concept that this approach can deliver a functional cure for HIV.

“Our goal is to be able to deliver these potent broadly neutralizing antibodies with one shot so the patient is good for life,” he explained. “But more research needs to be done.”

While such a technique—known as anti-retroviral drug therapy— may suppress viral replication in HIV-infected humans, or SIV- or SHIV-infected monkeys, the study’s authors say it is not a cure. Removal of antiviral drugs results in a rebound of plasma viral loads in the vast majority of individuals. Because of this, repeated infusions are needed to maintain a protective concentration.

In addition, while two other monkeys in the study also maintained long-term viral suppression, the AAV delivery method triggered a defensive immune system response which inactivated the antibodies. The muscle cell-produced antibodies were seen as foreign antigens, resulting in an anti-drug reaction, which can also occur in some patients receiving antibodies for treating Crohn’s disease, rheumatoid arthritis or other conditions.

“Now, we have to solve this anti-drug antibody problem so that we can generate a robust response in virtually all humans,” said Desrosiers, noting this could be a significant breakthrough for world health. “One advantage to this AAV approach is that it could be readily applied throughout the developing world, where antiretroviral therapies are not readily available. An easy ‘one-shot’ approach could make a huge difference in addressing this global epidemic.”

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