Local researchers unveiled a pioneering study this week that showed some patients with HIV were able to remain healthy, despite discontinuing their antiretroviral medication.
At the 2012 Conference on Retroviruses and Opportunistic Infections in Seattle Wednesday, scientists from Philadelphia’s Wistar Institute, Philadelphia FIGHT and other organizations presented results of a clinical trial that marked an important first in the fight against the HIV/AIDS epidemic.
In the study, HIV-positive individuals replaced their antiretroviral medications with interferon-alpha, an antiviral chemical produced by the immune system. While many studies have shown HIV viral loads increase and white blood cells decrease once ARTs are stopped, this study found viral loads in many of the patients remained under control and HIV reservoirs — the cells that harbor the virus — were able to decrease with the interferon.
“Our data shows that our human immune response can be made to control HIV in persons who have otherwise lost that ability and, if sustained by natural interferon production, it establishes proof-of-concept that a functional cure is theoretically possible,” said Dr. Luis Montaner of Wistar Institute.
Interferon is created by the immune system to inhibit viral replication in cells, but the natural form of the chemical is not strong enough to successfully function as an antiviral tool against HIV.
“When someone is first infected with HIV-1, the immune system is overwhelmed, and the natural release of interferon into the bloodstream is ineffective as cells that produce it are quickly impaired,” Montaner explained. “But in our study, conducted at a later stage of chronic infection in an individual, we saw that adding interferon to a recovered immune system can have a dramatic effect in directing responses against HIV-1 to both control and reduce its detection within places we know it can hide.”
The form used in this study was created through the addition of polyethelyne glycol to the interferon molecule, a drug approved several years ago to fight hepatitis.
Study catalyst
FIGHT executive director Jane Shull said the hepatitis connection set this latest study in motion.
“A few years ago, Luis said that they have this situation where interferon seems able to control a virus, namely hepatitis C, and it had been given to a lot of people with HIV because so many are co-infected,” she said. “So Luis said we’re going to see if it can also control HIV. And then it worked so much better than anyone thought it would.”
Twenty patients were involved in the study, identified through FIGHT, Drexel University and University of Pennsylvania.
Of the 20 participants, 45 percent were able to sustain viral control under 400 copies per milliliter and a similar percentage saw a 50-percent reduction in HIV reservoirs.
Montaner said researchers were “surprised to see patients maintain the gains made through ART using only interferon that modulates our body’s response rather than acting directly against HIV as all current HIV drugs do.”
The trial lasted up to 24 weeks or until a patient’s HIV levels rose or CD4-T cell level dropped below a certain level. Even those whose levels fell out of range before the 24 weeks had better results than the control group, researchers noted.
Montaner acknowledged that while the findings “may not immediately change clinical practice,” they represent “the first strategy that shows a clinical response where both viral replication and HIV reservoir indicators are observed to be reduced in absence of current chemotherapy. This is the type of response HIV cure research aims to achieve.”
“We’re actually moving toward eradication,” added Shull. “This is going to change everything.”
Shull said the next step will be constructing a larger trial to evaluate interferon effects in a wider pool of patients.
Funding for this study came from national resources as well as The Philadelphia Foundation’s Robert I. Jacobs Fund, the Stengel-Miller family, HIV/AIDS funding from the state of Pennsylvania, the Pennsylvania Department of Health, the Commonwealth Universal Research Enhancement Program and Penn Center for AIDS Research.
In addition to Wistar and FIGHT, authors of the study are from University of Massachusetts, University of Pennsylvania, Drexel University, Blood Systems Research Institute, University of California and National Cancer Institute.
Jen Colletta can be reached at [email protected].
