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Combating HIV: The future of therapeutic vaccines

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HIV patients rely on an array of drugs to keep their illness under control, sticking to a strict regimen to maintain health. Today, there are 31 FDA-approved anti-retroviral drugs used to suppress the virus, sometimes even to undetectable levels, according to NIH.

But let's face it: Adherence is a challenge and drug side effects can be rough. For anti-retrovirals to work effectively, patients must take the drugs at least 95% of the time. And, though the average rate of adherence varies by the method used to assess it and the group studied, adherence to anti-retrovirals hovers around 70%, according to a University of California, San Francisco, report.  Enter HIV therapeutic vaccines.

The last intense wave of interest in HIV therapeutic vaccine research ended in a flop with sobering results from the Strategic Management of Antiretroviral Therapy trial. Researchers halted the trial after only two years, despite a planned runtime of 9, after the discovery of risks of the interruption strategy. Investigators sought to recruit 6,000 patients who they divided into two groups: One received continuous anti-HIV treatment and the other got intermittent treatment on the basis of CD4 cell counts. Those in the latter group stopped receiving treatment when their CD4 cell count rose above a certain level and started treatment again when that number dropped too low. The idea, researchers said, was to help patients maintain CD4 cell counts at a safe level while minimizing anti-retroviral drug side effects.

Researchers nixed the study Jan. 10, 2008, when they discovered intermittent treatment upped the risk of disease progression, AIDS and death.

Still, biotech has yet to give up on HIV therapeutic vaccines as a means to curb or eliminate the disease. A major focus, said Richard Jefferys, the basic science, vaccines and prevention project coordinator with the Treatment Action Group, in his paper "The Odyssey of Therapeutic Vaccines for HIV," is identifying and eliminating the HIV-infected cells that crop up and continue to do damage despite anti-retroviral drugs. The question researchers are trying to answer now is whether it's possible to come up with a therapeutic vaccine to generate HIV-specific immune responses capable of fully containing viral replication when anti-retroviral drugs are interrupted. Put simply, either find a way to prevent the disease when a patient isn't on drugs, or eliminate the virus entirely with a cure.

Several companies are taking a varied approach to arm the body's immune system with a way to recognize and battle the virus to, hopefully, minuscule levels. Argos Therapeutics, for example, is taking white blood cells from patients and inducing them to become immature dendritic cells. Those cells are then exposed to the RNA of HIV particles taken from the patient until they produce antigens. When reintroduced into the patient, the antigens can use T cells to find and kill HIV. The candidate is dubbed AGS-004.

And Bionor is working on Vacc-4x, which trains the body to identify and fight a protein, p24, on which HIV relies. The vaccine consists of four peptides and trains immune cells to seek out and kill cells carrying HIV. The candidate targets what are known as "conserved domains," or the parts of HIV that are consistently present, even as the virus mutates. Sustained immune responses to this part of the virus--the HIV protein p24--have been shown to delay HIV disease progression.

Some researchers believe that conquering HIV will require a combination of anti-retroviral drugs and a therapeutic vaccine. One interesting ongoing trial taking this approach is EraMune 02, with collaborators Objectif Recherche VACcin Sida, National Institute of Allergy and Infectious Diseases, Pfizer ($PFE) and Merck ($MRK), and funded by the Bettencourt Schueller Foundation. The clinical trial focuses on attacking latent virus hiding out in viral reservoirs through a more rigorous anti-retroviral regimen and an investigational vaccine that can activate cells infected with HIV to develop a disease-fighting response to the virus' DNA.

Despite failings in the past, HIV therapeutic vaccines still prove a worthwhile research area. Going forward, researchers should explore various combinations of treatments, Jefferys said.

"Researchers also need to explore which other anti-latency strategies should be combined with therapeutic vaccines, and whether different vaccine candidates should themselves be combined to achieve the best results," Jefferys wrote. -- Alison Bryant (email | Twitter)