The challenge of finding a cure for AIDS may have gotten harder. Scientists have discovered another cell in the body where HIV — the virus that causes AIDS — hides from therapy designed to suppress it to undetectable levels in the blood.

The cells — called macrophages — are part of the immune system and are found throughout the body, including in the liver, lungs, bone marrow and brain. After other immune cells have done their job of destroying foreign invaders, these large white blood cells act as the cleanup crew. They surround and clean up cellular debris, foreign substances, cancer cells and anything else that is not essential to the functioning of healthy cells. In addition, they apparently can harbor HIV.

A new target

While antiretroviral drugs can drive the AIDS virus down to virtually undetectable levels, scientists know if therapy is interrupted, an HIV infection can come roaring back. That’s because of a viral reservoir that until now has been thought only to inhabit immune system T-cells — the cells that are attacked and destroyed by the AIDS virus. Much research is dedicated to trying to find ways to eradicate the T-cell reservoir.

This may mean researchers must find ways to eliminate HIV from macrophages, as well.

The finding was published in Nature Medicine by researchers in the Division of Infectious Diseases at the University of North Carolina School of Medicine. 

Investigators demonstrated in a mouse model that in the absence of humanized T-cells, antiretroviral drugs could strongly suppress HIV in macrophages. However, when the therapy was interrupted, the virus rebounded in one-third of the mice. This, say researchers, is consistent with persistent infection in the face of drug therapy.

Researchers say their work demonstrates that any possible therapies must address macrophages in addition to T-cells to eradicate viral reservoirs. Investigators say they now have more information pointing to the complexity of the virus, and that targeting the viral reservoir in T-cells in the blood will not necessarily work with tackling HIV persistence in macrophages, which reside in tissues and are harder to observe. 

Senior author Victor Garcia said it’s possible there are other HIV reservoirs still to be discovered.

The lead author of the study, Jenna Honeycutt, called the discovery “paradigm changing” in the way scientists must now try to eliminate persistent infection in HIV-positive individuals. 

Investigators say their next step is to figure out what regulates HIV persistence in infected macrophages. They are also interested in finding HIV interventions that completely eradicate the AIDS virus from the body.
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