THE LONG ROAD TO SUCCESS

What We’re Learning: It’s more difficult than we realized to design scientifically rigorous clinical trials for HIV prevention.

We are committed to the idea that the best way to fight HIV/AIDS is not just to treat people who already have it, but to find ways to prevent people from getting it in the first place. Last year, however, was a year of frustration for the HIV prevention field. Clinical trials testing diaphragms, herpes suppression, one vaccine candidate, and several microbicide candidates did not show any of these interventions or candidates to be effective in preventing HIV infection.

We funded the diaphragm trial and helped with the microbicide trials.

Researchers considered diaphragms a promising method of protection because they cover the cervix, where HIV infections are thought to occur in women.

Microbicides, topical gels that reduce the risk of contracting the virus, are thought to have good potential because they allow women to initiate prevention.

But last year two different microbicide candidates, Carraguard and cellulose sulfate, failed in trials.

Like everyone else working in prevention, we were disappointed with these results, but we are not discouraged. Scientific research and development is a high-risk endeavor. Negative results are expected; it’s part of the process.

In fact, failure is critical to success. When we discover what doesn’t work, we gain scientific knowledge that eventually will help us learn what does work. And the feedback from failures helps us continually set new priorities.

In the case of HIV prevention, we learned a couple of important lessons in 2007. First, we have to improve our planning of clinical trials, particularly as it relates to the problem of HIV “incidence.” Incidence is the rate of new infections that researchers will see in a given trial. Because it is difficult to predict incidence, planning the size and duration needed for a trial to show results is a challenge.

Second, we learned that we have to do a lot more to promote adherence to the product being tested. In the diaphragm trial and the microbicide trials especially, many women simply did not use the intervention. In the Carraguard trial, for example, adherence to the product was estimated to be less than 50 percent.

This is problematic for two reasons. First, it means we don’t know if an intervention failed because it didn’t work or because people didn’t use it. Second, as long as adherence rates are that low, even theoretically effective interventions won’t be practically effective. Even the best preventative method isn’t any good if it doesn’t get used.

Potential ways to improve adherence include educating people about the benefits of effective prevention measures or better monitoring people as they use them.

As we look ahead, several new methods are slated for clinical trials in the next few years. A new generation of microbicide candidates—ones that are more potent because they include antiretroviral drugs that attack the virus directly—are being developed for testing in large trials.

In addition, we are helping to fund trials of Truvada, an AIDS treatment combination drug that may also help prevent infection.

Finally, we are funding an entirely different kind of herpes-suppression study. The two that failed last year studied whether people who took herpes drugs acquired HIV less frequently; this one studies whether people who take herpes drugs transmit HIV less frequently.

We know that some of these trials will also have negative results. That’s part of the scientific process. But they are all part of the long-term strategy for success.