Inside the HIV fight: from vaccines to microbicides, from preexposure prophylaxis to circumcision, researchers are considering multiple options in the fight to prevent HIV. Tim Murphy talks to the players involved and gives us a progress report.(HEALTH)

Though Scott Smith and Joe Birdsong are both gay, their differences outweigh their similarities. Smith, 39, is a clean- cut Atlanta IT sales rep, while the punk-coiffed Birdsong, 37, used to be a go-go boy and now owns the Rapture Cafe, a New York City hipster hangout. But two years ago they both joined about 3,000 HIV-negative volunteers for the final clinical trial phase of an HIV vaccine made by pharmaceutical giant Merck and Co.

Both say they joined the trial in part to honor friends who are living with or have died of HIV/AIDS. Says Smith, who is black: "I know they're always short of African-Americans to participate in drug studies." Birdsong says he saw being in the trial "as a way of me not feeling so powerless" against the epidemic.

It's easy to feel powerless against AIDS. Almost 40 million people are living with HIV or AIDS worldwide, the vast majority of them in sub-Saharan Africa and other poor regions. Internationally, nearly 14,000 people become infected with HIV every day, and in the United States, the majority of new infections are still occurring among gay and bisexual men, especially those who are African-American. No wonder Smith and Birdsong want to help prevent HIV infections once and for all.

But in late September they learned that the Merck trial would shut down roughly a year before its intended end date. Why? Examining data from just over 1,500 volunteers, researchers found slightly more infections in those getting the vaccine (24 of 741) than in those getting the placebo (21 of 762). Such numbers indicated not only that the vaccine was a lemon but that it might even promote HIV infection.

"Obviously, we're disappointed," says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which held the trial with Merck. And with good reason: Though more than 30 vaccines are in small, preliminary trials around the world,…