One of the most important quests in AIDS research—a gel that women could use to prevent HIV infection during intercourse—has suffered its second major setback in little more than six years.

Bereft of a cure or vaccine against a disease that has claimed more than 25 million lives in as a quarter century, scientists are doggedly pursuing the path of vaginal microbicides. These are creams that a woman would apply, rather like contraceptive spermicides today, to block or kill the AIDS virus.

To the dismay of the tight-knit community of microbicide scientists, two out of six advanced trials of candidate gels have been stopped for safety reasons, providing a reminder of the many unknowns and risks that hedge their work.