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Saturday, July 21, 2012

Towards an HIV Cure: Workshop Summary

The Global Strategy Towards an HIV Cure, developed under the auspices of the International AIDS Society by an international working group of researchers, aims to provide a road map for scientists, governments, funders, and industry to get the job done.
Dr. Steven Deeks indicated that "we need a fundamentally different way of approaching HIV infection."
In a summary of that meeting in The Lancet a new strategy was outlined. The new strategy outlines seven main priorities for research straddling basic, translational, and clinical science if either a “sterilizing cure”, which permanently removes the virus, or a “functional cure”, which controls it for years without drugs, is to be found.

Several routes potential routes for the eradication of HIV include use of aggressive drug regimens; early initiation of antiretroviral therapy (ART); use of virus-purging agents; enhancement of anti-HIV immunity; better understanding of basic HIV science; modification of host genetics; and use of HIV-specific killing agents. The report also highlights ethical challenges of the work, including the problem of undertaking clinical trials when the effectiveness of ART means that there is little benefit to volunteers from participating.
The so-called "Pathway to a Cure" requires the following priorities for researchers:
Seven main priority areas for research into an HIV cure
• Cellular and viral mechanisms involved in HIV persistence at a molecular level
• Anatomical compartments and cellular sources of HIV reservoirs
• Immune activation and dysfunction in the presence of antiretroviral therapy
• Natural models of HIV/simian immunodeficiency virus control
• Assays to measure persistent infection
• Therapeutic and immunological approaches for eliminating persistent HIV infection
• Enhancement of immune response to control viral replication

One drug candidate is vorinostat (Zoliza; Pantheon/ Merck), an agent used to treat cutaneous T-cell lymphoma. Vorinostat is in a class of medications called histone deacetylase (HDAC) inhibitors. It works by killing or stopping the growth of cancer cells. In HIV, the drug appears to cause the latent virus to be expressed.
A theoretical approach to a cure could be a four-part assault. One proposed treatment strategy would (1) use vironostate with (2) an anti-inflammatory drug to diminish the number of cells susceptible to infection, (3) a therapeutic vaccine to enhance the capacity of the immune system to kill those infected cells that are now making virus, and (4) intensified antiretroviral therapy to prevent any new cells from becoming infected.
Also highlighted in the strategy is gene therapy for HIV, which consists of taking cells from the patient, altering them so that they contain the CCR5 mutation and then expanding the number and re-infusing them into the patient with the hope that they will work as well as a naturally occurring CCR5 mutation.
Meanwhile, the new cure strategy is problematic for some researchers. The focus on only two options—medication with ART or a cure—could lead people to think that other, preventive approaches, which have been shown to work in the real world and require vastly less money, are not as important. “If you talk a lot about a cure and you get all this hype and excitement going it could make it harder for behavior change to happen on the ground," according to Daniel Halperin, University of North Carolina at Chapel Hill
Other experts see this as a milestone. This is the first consortium to lay out a pathway for a cure, says Bruce Walker, Harvard University and director of the Ragon Institute in Massachusetts—a collaboration which is working to accelerate the discovery of an HIV/AIDS vaccine. There are still many unknowns and challenges, but stating the goal is the “first step” towards achieving it. “We have to set a high bar for ourselves”, he says. “And once we figure out how to cure the virus we can turn our attention to doing it in a way that is going to be cheaper and more deliverable.”

Corbyn, Z. Plan launched to find HIV cure. The Lancet, 2012; 380: 203 - 204, 21 July 2012

Source: Reported for the PRN News by Bill Valenti, MD