Frist, of Tennessee, a physician and the panel's moderator, barely said a few words at the beginning of the hourlong discussion when more than a dozen protesters rose and moved to the front of the room, carrying red umbrellas and shouting "sex workers' rights are human rights."
The activists were protesting the global AIDS initiative started by former President George W. Bush, a program that provides HIV treatment to 4 million people worldwide, but excludes prostitutes, who account for a high percentage of HIV infections.
The group chanted for about five minutes before yielding the floor back to Frist.
"I'm used to this being majority leader," said Frist, who served two terms in the highly decorous Senate and rubbed his temples in frustration as the protesters continued to disrupt the event.
Sen. Mike Enzi, R-Wyo., was interrupted next. Enzi, who has made several trips to African countries affected by HIV, told the protesters that he had voted twice to renew the Ryan White Care Act, a federal law that extends HIV treatment to lower-income Americans and promised to do so again when it expires at the end of the year.
Rubio, a Senate freshman and potential Republican vice presidential candidate, also got shouted down.
Parting ways with many of his tea party supporters who want deep cuts in federal spending, Rubio said zeroing out AIDS funding, or any foreign aid, would do nothing to reduce the deficit, and would be "devastating" for the world. His home state of Florida has one of the highest rates of HIV infection.
"It's in the national interest of the United States to eradicate AIDS," he said.
The protesters went easier on the two Democrats who participated, Rep. Barbara Lee of California and Sen. Chris Coons of Delaware.