Investigational approach to AIDS treatment may allow patients to clear all HIV

Clinicians who care for patients infected with HIV are testing a new set of experimental treatments that may eliminate the hidden copies of the virus that previously have made a cure unattainable.

AIDS treatment centers, including the AIDS Clinical Trials Unit (ACTU) at the School of Medicine, are participating in the trial, which is recruiting people infected with HIV who have not yet begun taking anti-HIV treatments.

Treatments based on combinations of several different AIDS drugs have already transformed the immune deficiency caused by HIV from a fatal disorder into a manageable condition for many patients.

But while the “drug cocktails” taken by patients often reduce the HIV in their bloodstream to undetectable levels, the virus stashes hidden copies of itself that allow a renewed outbreak of infection if treatment ever stops. The copies are stored in the lymph nodes in cells such as the immune system’s memory T cells, which normally help the body’s defensive systems remember invaders.

Many years of treatment with anti-AIDS medications should eventually drive down this latent viral load, but researchers estimated that it would take at least several decades to clear the infection completely.

Impetus for the new trial came from the development of the drug T20, which can inhibit HIV at a different point in its life cycle than existing drugs. Scientists want to combine T20, which is commercially known as Fuzeon and blocks the virus’ ability to fuse with host cells, with other drugs to mount an intense assault on HIV.

“We hope it will be such a potent combination that the latent copies of HIV possibly could decay faster than what we see now with standard therapy,” said Lisa Mahnke, M.D., Ph.D., a principal investigator at the ACTU.

To replenish itself, the latent virus has to become active from time to time and make new copies of its genetic material. Scientists want to see if the new drug combination makes that step particularly difficult for the virus, leading to a decrease in its ability to maintain latent copies.

“If we can get decay time down to a reasonable time span, then we can talk about the possibility of a cure,” Mahnke said.

In the new trial, Mahnke and other researchers will give patients the aggressive treatment package for four years, using the latest detection and analysis techniques to closely monitor both the levels of virus in blood and the presence of latent virus, hoping to track how fast the latent reservoir decays.

Leading the trial is Robert Silicano, M.D., Ph.D., an AIDS researcher at Johns Hopkins University, who was the first to identify latent HIV and the formidable obstacles it presents to development of a cure.

Because of HIV’s ability to quickly develop resistance to AIDS medications, the trial is limited to people who have not yet begun treatment.

Potential participants will be tested prior to enrollment for medication-resistant mutations.

Nationwide, scientists are working to recruit 40 people who have been infected with HIV for more than six months; the ACTU will be seeking to enroll two people.

In addition to taking oral medications, patients in the trial will give themselves injections of T20 twice daily. They will also undergo standard blood draws on a regular basis and a larger blood draw about once every six months.

“It’s an intensive treatment and monitoring regimen, so we’re looking to find people who are highly motivated,” Mahnke said.

For more information or to volunteer, call Debra Demarco at 454-0058.