SOWETO, SOUTH AFRICA—The Perinatal HIV Research Unit (PHRU) at the sprawling Chris Hani Baragwanath Hospital here is abuzz with activity. Young women with swelling bellies wait in plastic chairs to see nurses while pharmacists distribute antiretroviral drugs from an office behind a metal security gate. Upstairs, a fresh coat of paint is being applied to the walls of a new men's clinic that offers HIV-testing, support and treatment.

In the late 1990s PHRU pioneered research into using antiretroviral drugs to prevent and treat HIV, the virus that causes AIDS, in developing countries. Today, it is a model of how funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)—more than $18.8 billion since 2004—has radically changed the global fight against AIDS and helped put more than 1.7 million people, mostly in Africa, on life-prolonging antiretroviral treatments who otherwise would likely have died.

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

The United Nations estimates that in 2007 (the latest year for which stats are available), 33 million people around the world were HIV-positive. Twenty-two million of those people are in sub-Saharan Africa. PEPFAR targeted 15 of the world's hardest hit countries in Africa, Asia and the Caribbean.

Once mostly a research institution, the PHRU now supports programs providing antiretroviral treatment for 30,000 HIV-positive people in four South African provinces and provides palliative care to some 30,000 others. In the township of Soweto, it has reduced the transmission rate of HIV from pregnant women to their newborns from about 25 percent in 2000 to around 5 percent today, protecting nearly 2,000 babies a year. The mothers and their infants are treated with antiretroviral drugs, meds designed to block viruses like HIV from replicating.

When Pres. Bush launched PEPFAR in 2003, pledging to give $15 billion over five years to fight global AIDS, many in the international AIDS community greeted the new program with skepticism. Critics slammed earmarks for abstinence-focused prevention programs and for expensive, brand-name antiretroviral drugs. The Bush administration was also hit for forking over only 16 percent, about $3 million, to the Geneva-based Global Fund to fight AIDS, TB and Malaria. The international community created the fund in 2001 to boost and coordinate funding for the three diseases.

But five years later, the program is widely viewed by development and public health experts as a success story. PEPFAR specifically is credited with helping to make antiretroviral therapy a reality in many of the world's hardest-hit countries. (Tests are now underway to see whether the drugs can also be used as a prophylaxis in HIV-negative people.)

"If we didn't have PEPFAR, we'd be lucky to have half as many people on treatment as we do at the moment," says Francois Venter, a physician and president of the Southern African HIV Clinicians Society in Johannesburg. "It forced everyone involved to be very focused on the endpoint: how many people tested, how many people treated," adds Venter, who also heads a PEPFAR-funded program at the University of the Witwatersrand's Reproductive Health and HIV Research Unit in Johannesburg.

Without PEPFAR, Norah Mahlangu insists her 10-year-old son might well be an orphan. The 27-year-old HIV-positive woman from Soweto is slowly crawling back from the edge of death with the help of Susan Moloto, a nurse at the Soweto Hospice whose annual salary is paid with PEPFAR funds. Moloto visits Mahlangu each week and has helped shepherd her patient through treatment for tuberculosis as well as enroll Mahlangu in an antiretroviral therapy program.

"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