"She helps me stay alive," Mahlangu said during a recent interview at her house, where she lives with her son, mother and other relatives.

But now that 1.73 million are receiving therapy through PEPFAR, many public health advocates believe it's time for the U.S. program to shift gears.

"I think the program is seeing that now the quality needs to improve, that it's not only about numbers," says James McIntyre, co-executive director of PHRU, which receives about 90 percent of its funding from the U.S. government. In the 2007 to 2008 fiscal year, the program received $14.76 million from PEPFAR.

There's renewed focus, too, on sustainability. Antiretroviral treatment must be taken for life and PEPFAR funds are not guaranteed to flow forever. Organizations that receive funding are being asked to start thinking about how their programs can eventually be integrated into national health care systems.

A new PEPFAR-sponsored 30-second TV spot aimed at young people in South Africa uses slang to warn of the dangers of multiple, concurrent sexual partners, which many researchers believe is a key cause of the HIV epidemic in Africa. "An undercover lover will bring you HIV from another," the ad's narrator warns, as the cartoon shows how HIV can move quickly through sexual networks.

PEPFAR's early days were marred by bitter debates between advocates of condom-based prevention strategies and those who favored an emphasis on abstinence and fidelity. In Uganda there were allegations that the program had contributed to an anti-condom agenda as well as acute condom shortages.

But in recent years, those divisions have become blurred as new research has netted increased knowledge about the roots of the epidemic.

"There's been a big shift from the ideological, early days of PEPFAR," says Richard Delate, director of the Johns Hopkins Health Education in South Africa program, which produced the animated anti-HIV public service announcement as part of an AIDS-prevention public-information campaign called "Scrutinize".

"Too many programs put prevention on a back burner, but there's a recognition that we've got to put it back on the public agenda," Delate says.

AIDS activists are optimistic that President-elect Barack Obama will eliminate the set-asides for abstinence-only programs. "We would want any kind of earmarking eliminated," says Jamila Taylor at the Center for Health and Gender Equity in Takoma Park, Md. "Country partners should be able to decide for themselves how best to address HIV/AIDS."

But despite overall optimism about PEPFAR, there's fear that the global financial crisis could lead the U.S. government to reduce its commitment to the program. Congress in July reallocated funds for the program, authorizing the U.S. to spend up to $48 billion over five years.

U.S. Global AIDS coordinator Mark Dybul, PEPFAR's top official, insists the U.S. is in this for the long run.

"I don't think there's a question," he says, "that this program will have to continue beyond five years."

Slide Show: AIDS Care: PEPFAR delivers drugs—and results

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