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Advances in HIV research provide hope

BY JEROME A. ZACK

Will HIV infection ever be cured?

Although a cure has thus far eluded us, we shouldn’t lose focus on believing that a cure for HIV, the virus that causes AIDS, is still possible.

Physicians can now treat HIV-infected patients with highly potent medications that dramatically reduce the levels of virus in the blood, and lessen symptoms of AIDS. However, these drugs do not completely eliminate HIV from the body.

In addition, the drugs themselves can make the patient very ill, so that they must stop taking the medications. But if a patient discontinues their treatment, even if they previously had no detectable HIV in the blood, virus levels rapidly rise, and symptoms of the disease reappear.

This new burst of virus is kindled by a small number of infected cells that contain dormant or “latent” virus. Latent virus exists at very low levels in certain blood cells called T lymphocytes. Current treatments have little, if any, effect on latent virus, and physicians estimate that it would take more than 70 years to eliminate latent HIV from the body. However, we must eliminate all of this virus if we ever hope to cure this disease.

A new strategy that might eliminate latent virus involves slight activation of the infected cells, causing the latent virus to “wake up” so that it could be detectable by the body’s immune response. This would have to be done carefully, since over-activation of T cells could actually impair the immune system.

Our lab has developed a model where cells latently infected with HIV can be easily studied. We have used this model to identify a new approach to attempt to eliminate latent HIV. We have found two substances that only slightly activate T cells, but the virus is turned on so that it is no longer latent. This forces the virus to make proteins that then appear on the surface of the cell.

We next added a molecule called an “immunotoxin,” which is part antibody and part bacterial toxin. The immunotoxin works like a smart bomb; the antibody portion recognizes and binds to the viral protein present on the cell, but does not bind to uninfected, normal cells. The toxin, which is attached to the antibody, then enters and kills the infected cell before the cell can produce more viruses. Using this approach we eliminated up to 80% of latently infected cells.

While this approach is still years away from being tested in infected patients, it provides proof-of-concept that latently infected cells can be eliminated without harming normal cells. There are other types of cells in the body that could contain latent virus. Thus, to fully eliminate HIV, these other sources of virus must be identified and systematically targeted.

Our recent work, however, provides a hope that physicians may eventually be able to eliminate these hidden sources of virus. This might allow HIV-infected patients to stop taking their medications without rebound of virus replication, effectively resulting in a “cure.” We hope to move as quickly as possible to begin testing this approach in patients.

In the meantime, until there is a cure, scientists and physicians must continue to develop improved and safer anti-viral therapies. Since the incidence of HIV infection is on the rise again, as a global society we also need to concentrate on prevention strategies and education efforts aimed at high-risk populations. Together, these efforts could put an end to this epidemic forever.

Zack is associate director of the UCLA AIDS Institute and a professor of medicine, and of microbiology, immunology and molecular genetics.