AIDS Vaccine 2013: Four years on, surprise success of Thai trial buoys field

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aidsvaccine2013Science Speaks is live-blogging from AIDS Vaccine 2013 this week. Meeting in Barcelona, Spain, with the theme “Progress, Partnership and Perserverance,” from Oct. 7 to Oct. 10, this event brings together a history of hope, and an update on opportunities that have shown themselves in recent years.

BARCELONA, SPAIN – In a field as complex and apparently Quixotic as the quest for an HIV vaccine, analogies abound (“The virus is Machiavellian,” HPTN 505 researcher Scott Hammer says, while another calls the search for a vaccine against the ever mutating virus “an arms race.”)  This week comparisons have lighted on the architecture of Barcelona with its towering cathedrals and the beauty of its mosaic embellishments. The foundations of the old cathedrals here were not laid with the expectation that the building would be completed in one’s lifetime, after all. And the art of the mosaic came from the careful placing of broken pieces, Global HIV Vaccine Enterprise leader William Snow points out. They are analogies that the story of RV-144, the legend now, of the field, supports.

In 2009, its most recent hopes dashed by a halted clinical trial that had offered the disquieting data two years earlier indicating those taking the product fared worse than those taking a placebo, the field of HIV vaccine research had little to look forward to.

Then, outta nowhere — a Cinderella story.

The results of a clinical HIV vaccine trial in Thailand, which many in the field had said should not even take place, and from which few expected news, showed for the first time in Sept. 2009, that the risk of HIV infection could be reduced by a vaccine. Four years on, while still unfailingly described as “modest,” the results of the U.S. Military HIV Research Program’s RV 144 trial and the proof of concept they offered, continue to offer hope to researchers gathered here, even as they explore an increasing diversity of approaches to a vaccine that offers a greater degree of protection from the virus that leads to AIDS.

Expectations were low for RV 144 even before it began, Dr. Merlin Robb says, because it followed a tactic similar to that of the VaxGen trial, which had just concluded and been found ineffective. It came close to not even taking place for that reason, but everything was in place, it would produce data, and would do no harm, researchers reasoned.

Merlin RobbThe trial built on something that had failed, but added new elements, Dr. Merlin Robb explains. What even the initial results indicated that what it added made a difference — a “modest” 31 percent difference of lowered HIV incidence among those taking the investigational product as opposed to those taking a placebo. Findings since have been even more encouraging — first lab evidence of immune responses in those taking the product, and then evidence that the product changed the virus.

“It meant a lot,” Robb said.

Now some here are asking what’s taking so long. Why isn’t another clinical trial using what was learned from RV 144 already underway? At the same time Snow of the Global HIV Vaccine Enterprise says it seems to be moving along well, that researchers appear to be making “the best possible effort.”

Snow knows how the vaccine field works, Robb says. Also he adds, with little expectation that RV 144 would succeed, and little understanding of why it did, “We were caught flat-footed,” Robb adds.

There remains much to explore. The original trial worked with a population of relatively low HIV incidence, leaving open the possibility that the product was not sufficiently challenged in the early period the trial during which a disproportion number of HIV acquisitions can take place. The immune enhancing advantage dwindled after 12 months.

The next trial will be in Southeast Asia, in a high risk population of men who have sex with men and transgender individuals, Robb said.

Researchers are focused on replicating the results in a larger trial, improve the durability of the effect and on adding an approach to enhance the protection to a level — beyond 31 percent — that would make an eventual licensed product promising.

In the meantime, Robb, who works for a contractor, rather than directly for the U.S. Government, is busy in Barcelona, while his U.S. Military HIV Research Program colleagues with leading roles in the research are sidelined in the states by the continuing Congressional government shutdown.

“It’s awkward,” he says, ” to be here representing people who I think should be presenting their own data. I am sure they would like to be.”


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