The Next Great Hope for an HIV Vaccine

RV144, an experimental HIV vaccine at the center of the largest human AIDS trial to date, is the first to show a significant result in HIV prevention.

The study, a joint effort between vaccine patent-holders and U.S. and Thai governmental agencies, involved more than 16,000 Thai volunteers -- half who received six doses of the vaccine in 2006, half who received a placebo.

Though RV144 was shown to be only 31% effective against infection, the trial results left researchers stunned and renewed hope that a vaccine against the deadly disease is still possible.

In a brief interview, Advocate.com spoke about the findings with Mitchell Warren, executive director of AIDS Vaccine Advocacy Coalition.

Advocate.com: How does the RV144 study differ from past studies that showed no significant evidence of protection against HIV infection?
Mitchell Warren: Previous efficacy studies looked at either antibody response or a cellular [CD4- or CD8-cell] response. This trial was the first large-scale efficacy trial to try a prime-boost combination vaccine, one meant to stimulate both cellular and antibody responses.

What's the bottom line of this study?
It's the first time we've had any significant positive result for a vaccine. We've always fundamentally believed that a vaccine is possible, but the clues have always come from various animal studies, elite controllers [people who are infected with HIV but never develop symptoms of AIDS], and highly exposed uninfected individuals.

But this is the first real evidence that a vaccine can provide protection from HIV.
It was an unexpected result by any estimation in a field with so many setbacks and scientific challenges. And it's pretty damn exciting. But now the real work begins in trying to understand what happened in the trial. There's a long road ahead of us in translating a clinical result into any kind of public health impact. Thirty percent is unprecedented, but it's not good enough.

What percentage would be a viable threshold for a vaccine to be approved?
That's a decision to be made by regulatory agencies in each country or region -- in the U.S., it's the FDA. And the regulatory bodies consider a wide range of data, not just the percent effectiveness coming out of a trial. But the conventional wisdom is that a vaccine should have no less than 50% efficacy, though a range of 60 to 70 percent is more promising.

Where do researchers go from here?
The scientific, policy, and advocacy communities need to work quickly, cooperatively, and boldly to translate these results into development of a scientific action plan, a plan for community engagement in Thailand and around the world, and a broader communication effort to convey both the promise and limitations of this result.

We all need to pore over the data to understand it better, which will take quite a while. Next month at the AIDS Vaccine Conference more data will be presented. In the next three to six months, we'll learn more about what this vaccine actually did.

Those who were given the vaccine and still seroconverted during the trial [a result of risk behaviors, not the vaccine itself] were given the option to enroll in another study that looks at long-term effects of the vaccine on viral load, disease progression, and drug interaction. Data from this study should give us even more good information to help understand how the vaccine worked.

Finally, this vaccine was matched with two subtypes of HIV common in Thailand: subtypes E and B. In the U.S., subtype B is more prevalent. The trial shows us that when the vaccine is developed and matched with a specific circulating strain, 30% of people are protected. But how would the vaccine used in the study affect a mismatched strain? We don't yet know.