New Initiative to Take HIV Down for the Count

The U.S. National Institutes Health is set to dole out $70 million in a new push to find ways to eliminate HIV, the virus that causes AIDS, from the bodies of people living with the virus, reported Science on July 11.

The money will go to three projects over the next five years. It represents the largest single funding initiative aimed at scrubbing the virus from the human body.

HIV is difficult to root out of all of the body's tissues. The virus can lie dormant in hard-to-reach places until years later. For this reason, it had long been thought that there might never be a way to completely eradicate the virus from a person who had become infected.

But the case of Timothy Brown, an American survivor of a bone marrow transplant to treat leukemia who seemingly was cured of the disease as a result, had caused scientists to reconsider. Brown was given marrow from a donor with a natural resistance to HIV. To receive the donated tissue, Brown needed to stop taking his HIV medication. To the astonishment of his doctors, no detectable viral presence appeared in his body following the procedure.

This does not necessarily mean that there are not still particles of the virus lurking in Brown's body. But if the donor's natural resistance to HIV was conferred upon Brown in a lasting way, it might not matter: Whatever remaining viral particles are possibly lingering in his system might never become active enough to build up a detectable viral load.

Such a treatment could be a boon to HIV patients who would otherwise rely on expensive medications for decades, living with the possibility of viral breakthrough (when the virus becomes resistant to a previously effective treatment) or long-term side effects from the medication. Cash-strapped governments could also see a savings if fewer people need to be kept supplied with the current standard cocktail of medications.

The medical procedures that Brown underwent to destroy his own bone marrow and replace it with donated tissue are grueling and expensive. Moreover, it is impractical to hope to treat thousands or millions of people by finding suitable donors with the mutation carried by Brown's donor.

The trick is to figure out a way to achieve a similar result more reliably, cheaply, and easily. That means looking into new approaches to fighting the virus where it lives -- in the body itself. But such approaches must be non-destructive to the body's systems, as well as thorough in stamping out or suppressing the virus.

One group of collaborators set to be funded by the new grant hopes to develop new medications with such small molecular structures that they can penetrate to the body's most hard-to-reach niches and wipe out any HIV residing there. The group, based at the University of North Carolina, Chapel Hill, is slated to receive more than $6 million per year for five years.

One of the other groups is set to investigate the possibility of engineering suitable marrow tissue for a similar transplant procedure to the one that seemingly cured Brown. The advantage to this approach is that a person's own stem cells could conceivably be modified to create marrow with the necessary properties, rather than hoping to find donors with naturally occurring mutations.

The third project will also pursue small-molecule treatments, the article said, while also using "immune-based treatments."

"The three collaboratories are using very different but largely complementary approaches," said one of the project's leaders, Steven Deeks of the University of California, San Francisco. "Since many of us believe a cure will require combination therapy, it is my hope -- as well as the hope of others -- that three groups can merge their work whenever possible."

Some of the ideas on the table have already been shown to have significant therapeutic potential. Researchers in Barcelona used patients' own cells to create a treatment that reduced the viral load in people living with HIV. Though they said that the reduction in detectable levels of the virus was "significant," researchers cautioned that at this stage the new treatment had not succeeded in dropping patients' viral loads to the point of not being detectable, as current HIV medication regimens do for many.

"However this is a very important improvement with respect to previous initiatives where with a similar vaccine there was a modest response in 30 percent of the treated patients," a statement from Hospital Clinic in Barcelona, where the clinical trial took place, said last February, and involved two dozen AIDS patients. "No therapeutic vaccine has achieved up to now the same level of response as in this study."

Cells from each patient's own immune system were used to create tailor-made doses of the vaccine.

The innovation of using patients' own cells to fight the virus comes at roughly the same time as news of another new approach, the use of specially engineered RNA that suppressed the ability of the virus to replicate itself. Suppression of viral replication is seen as one key component in the search for a vaccine or even a cure. Selectively targeting and destroying infected cells, while leaving healthy cells alone, is another.