Nearly 40 million people are living with HIV/AIDS worldwide. The vast majority reside in developing countries where medications to treat the virus are often either unavailable locally or unaffordable. An estimated 14,000 new cases of the disease occur every day. While a vaccine may be the best hope for conquering the epidemic, significant challenges remain ahead. Ever since HIV, the virus that causes AIDS, was identified more than 25 years ago, scientists have been trying to unlock its secrets. Their research has recently led the National Institutes of Health into large-scale vaccine trials worldwide. Gary Nabel is director of the Vaccine Research Center at NIH. He says the purpose of the so-called T-cell vaccines trials is to induce a cellular immune response that would both reduce levels of the virus and also preserve cells critical for protection against infection. He says within five years researchers will know whether or not the approach works. "If it does it will be important for us because it is an area that we can improve upon, and it's an area that we have lots of room to make progress." Nabel says another promising avenue for vaccine exploration has been to use antibodies that can fight or neutralize the HIV virus. "If we can make progress there then we really have some great opportunities ahead of us." Nabel says what makes an AIDS vaccine so problematic is the HIV virus itself, which is constantly mutating. "We're not really making a vaccine against a single virus, we are really making a vaccine that has to protect against millions of different viruses." Nabel says the virus also has an extraordinary ability to evade the human immune system, which is why developing broadly neutralizing antibodies to fight HIV has been so difficult. "And part of the reason for that is the protein on the surface of the virus that is the target of those antibodies not only differs in sequence among different viruses, but even on any given virus." Nabel says, "The virus is always lopping around and changing its shape on the surface making it a moving target." Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, says the trial vaccines won't provide blanket protection. But he notes that if they are successful, they will alter the disease by lowering the population of the virus and slowing its proliferation. "Ultimately this may and likely will have a positive effect in decreasing the efficiency whereby those infected people infect other people." Fauci says this approach combined with neutralizing antibodies that prevent infection could be the first big step towards an HIV vaccine. An estimated 20,000 volunteers are participating in trials in 24 countries. But science alone cannot conquer the AIDS epidemic. Advocates for a vaccine say it will also take financial support, political commitment, private-sector involvement, and greater attention to the economies and health care systems of developing countries.