Interferon Decreases HIV-1 Viral Levels and Controls Virus after Stopping Antiretroviral Therapy in Patients
Wistar Scientist Presents Results from Clinical Trial at 2012 Conference on Retroviruses and Opportunistic Infections
Interferon Therapy in HIV-1 Patients: Detailed Version from The Wistar Institute on Vimeo.
PHILADELPHIA - (March 7, 2012) - A multi-institutional
team of researchers, led by The Wistar Institute, has announced the results of a clinical trial that shows how the immune system can
engage in fighting HIV infection if given the right boost. In their study, HIV-infected volunteers suspended their daily
antiretroviral therapy to receive weekly doses of interferon-alpha, an antiviral chemical produced by the human immune
system. The study provides the first clinical evidence for a means of reducing the persistent amount of HIV in
patients and the ability to control HIV without continued antiretroviral therapy.
Wistar's Luis J. Montaner,
D.V.M., D.Phil. , today presents their findings of the first clinical strategy able to harness host control and decrease HIV reservoir
measures, at the 2012 Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. HIV reservoirs are populations of
cells that harbor HIV-1, enabling the virus to persist as a chronic infection.
"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 Montaner, a professor at Wistar and director of the Institute's HIV-1 Immunopathogenesis Laboratory."And while we still
have much to pursue with this early clinical finding, I firmly believe this gives us hope that one day we can control-and
eventually eradicate-HIV in absence of antiretroviral therapy."
The trial showed that interferon-alpha when used as a drug (Peg-IFN-a2A) sustained control of HIV in 9 of 20 patients while also
decreasing measures of HIV reservoirs in patients otherwise dependent on antiretroviral therapy (ART).No other clinical strategy
to date has shown an impact on decreasing integrated HIV DNA levels in HIV-infected humans.
"While our data may not immediately change clinical practice, it identifies 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," Montaner said.
"This is the type of response HIV cure research aims to achieve."
The study analyzed 20 patients over a period of 24 weeks. Remarkably, 45 percent of these patients were able to sustain viral
control under 400 copies per mililiter and a similar frequency showed more than 50 percent reduction in circulating
HIV reservoirs, as measured by the laboratory of Una O'Doherty, M.D., at the University of Pennsylvania. According to the researchers,
these results show that our immune system, which is targeted by the HIV-1 virus, can mount a defense to HIV infection, if given
the right stimulation.
"In previous studies, we have seen that when people suspend ART, their viral loads begin to creep upward while their white blood
cell count gradually drops," Montaner said. "We expected to see the same thing during this trial, but we were, frankly,
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."
"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 said. "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."
Patients were recruited in partnership with local HIV/AIDS clinical treatment programs, including the University of Pennsylvania,
Drexel University, and the Philadelphia Field-initiating Group for HIV Trials Philadelphia (FIGHT). The trial followed the
progress of 20 men and women of various ethnicities as they started on either of two different doses of interferon on
ART, discontinued ART, and maintained interferon treatment for up to 24 weeks. The trial lasted either 24 weeks or
until either their HIV-1 levels rose or CD4 T cell counts dropped to a pre-determined level, at which point they
would resume ART. Surprisingly, at midpoint (12 weeks), 45 percent (9 out of 20) of the patients still controlled
viral replication, and those that dropped out still compared favorably to the controls. Eight patients remained
in the trial during the entire 24 weeks. Both dosage arms achieved similar results.
"It is exciting to show control against HIV-1 can be regained by way of stimulating natural mechanisms," Montaner said. "Our findings also
open the way to determine if we can move this clinical research strategy towards a cure based on the decrease in HIV reservoirs we
Interferon-alpha is a chemical naturally manufactured by the human immune system to "interfere" with the ability of viruses to
replicate within cells. Since human interferon does not persist long enough in the body to serve as a useful antiviral drug,
pharmaceutical researchers modified it by adding polyethelyne glycol (PEG) to the interferon molecule, making it last
longer in the bloodstream with less toxicity. This "pegylated" form of interferon was approved in 2008 to treat
hepatitis B and C infections.
Funding for this research was provided through grants from the National Institute of Allergy and Infectious Disease of the National
Institutes of Health. Genentech/Roche also supplied support in the form of the Peg-IFN-a2A. Additional support was
provided by The Philadelphia Foundation (Robert I. Jacobs Fund), The Stengel-Miller family, AIDS funds from the
Commonwealth of Pennsylvania and from the Commonwealth Universal Research Enhancement Program, Pennsylvania
Department of Health, and the Penn Center for AIDS Research.
The lead author of the study is Livio Azzoni, M.D., of the Montaner laboratory. Co-authors also include Emmanouil Papasavvas, Ph.D.,
of Wistar; Andrea S. Foulkes, Sc.D., of the University of Massachusetts, Amherst; Ian Frank, M.D., Kenneth M. Lynn, R.N., Angela M. Mexas,
Ph.D., Una O'Doherty, M.D.,Pablo Tebas, M.D., and Jay Kostman, M.D., of the University of Pennsylvania Health System; Karam Mounzer,
M.D., of Philadelphia FIGHT; Jeffrey M. Jacobson, M.D. of Drexel University; Michael P. Busch, Ph.D., of Blood Systems Research
Institute; Steven G. Deeks, M.D., University of California, San Francisco; and Mary Carrington, Ph.D., of the National Cancer
Watch video of Montaner explaining the clinical trial here (short version) and here (long version).
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine
development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long
held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure
that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's
Discoveries - Tomorrow's Cures. On the web at www.wistar.org .
Contact: Greg Lester
The Wistar Institute