Elusive secret of HIV long-term immunity

Scientists have discovered a critical new clue about why some people are able to control the HIV virus long term without taking antiviral drugs. The finding may be useful in shortening drug treatment for everyone else with HIV.

These rare individuals who do not require medicine have an extra helping of a certain type of immune protein that blocks HIV from spreading within the body by turning it into an impotent wimp, Northwestern Medicine® scientists report. The new finding comes from analyzing cells from these rare individuals and HIV in the lab.

Scientists have been trying to solve the mystery of why 1 percent of people with HIV - called "controllers" - have enduring control of the virus without medications, in some cases for life. The controllers' early defense against HIV is quickly extinguished by the virus, so how do they have long-term immunity? The Northwestern discovery represents what scientists have long sought: a second line of defense deep in the immune system backing up the short-lived early defense.

This discovery suggests a novel approach involving much earlier treatment that could potentially make every HIV-infected person into a controller for the long term by protecting the reserves of this defensive immune protein. The goal would be for them to eventually be free from anti-retroviral drugs.

Currently most HIV patients need to take powerful anti-retroviral drugs every single day for life. If the medicines are stopped, the virus quickly reactivates to harmful levels even after years of treatment.

"Preserving and even increasing this defense in cells may make more HIV-infected persons into controllers and prevent HIV from rebounding to high and damaging levels when anti-HIV medications are stopped," said Richard D'Aquila, M.D., the director of the Northwestern HIV Translational Research Center. He is the senior author of the study, which will be published Oct. 16 in the journal PLOS ONE.

D'Aquila also is the Howard Taylor Ricketts Professor of Medicine at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital.

D'Aquila and colleagues now are working to develop a medicine that would boost this defensive immune protein called APOBEC3G, or A3 for short.

The Missing Second Defensive Line

Much is known about how the immune system of controllers initially fights the virus. But HIV quickly escapes from that first line of defense by mutating and evading the adaptive immune system. How these individuals control HIV long term without medications to keep from developing AIDS has been under study by many researchers. It seemed there must be a second defensive line in the immune system.

Turning HIV Into a Wimp

In the new study, D'Aquila and his team have found that controllers, long after they have acquired HIV, have a more abundant supply of the critical immune protein A3 in specific white blood cells called resting memory T cells. This is where the virus lies silently in an inactive form and roars back when anti-retroviral drugs are stopped. In controllers, though, their bounty of A3 means that any new HIV made from those cells inherits a helping of A3, which turns the new viruses into harmless wimps that can't infect other cells.