Late Sunday afternoon, less than a mile from the White House, the U.S. will witness something that it has not seen in 22 years: the opening of an International AIDS Conference.

The meeting, which this year is expected to draw about 25,000 scientists, activists and celebrities, has been held abroad for two decades because in 1987 the U.S. Senate unanimously passed a measure preventing anyone with known HIV infection from entering the country. At the time, the gathering—launched in 1985, four years after the first recognition of cases in the U.S.—alternated every year between U.S. and foreign locations. The 1990 conference in San Francisco, the first held after the rule was finalized, was gravely disrupted by thousands of delegates who stayed away—so much so that Harvard University, set to be the next U.S. host, announced it would withdraw its sponsorship unless the ban was lifted. It was not. The 1992 conference moved instead to Amsterdam, and the annual meeting stayed away until President Barack Obama lifted the travel ban in late 2009.

So much changed in that 22-year span that the conference’s return effectively marks a truly new phase in the epidemic. The latest report from UNAIDS, the United Nations agency that monitors the global epidemic, backs up the sense that things are changing. The report, released Wednesday, found that among the 34.2 million people living with HIV, fewer are dying: There were 1.7 million deaths last year worldwide, compared to 1.8 million the year before and a peak of 2.3 million in 2005. At the same time, the report said, new infections are declining too, by almost 20 percent in the past 10 years.

Simultaneously, after many years of disappointments, research is returning hopeful results for both prevention and treatment. Three years ago, scientists reported the first promising findings in the search for an HIV vaccine, considered the key to global eradication. Two years ago, researchers published the first partially successful trials of both a microbicide and a drug cocktail that may prevent infection. Last year, a nine-country trial demonstrated that getting infected people into treatment very quickly can keep them from passing the disease along. And since 2007, scientists have been closely watching the "progress of the “Berlin patient"—the only person, out of 60 million believed to have been infected in more than 30 years, who appears to have been cured of HIV.

The situation now is so different from 1990—when AIDS was a fast-moving, terrifying and invariably fatal disease, as captured in the new documentary How To Survive A Plague—that two HIV researchers writing in this week’s New England Journal of Medicine daringly titled their editorial: "The Beginning of the End of AIDS?"

For anyone who remembers HIV's apocalyptic arrival—I’m one of them, and lost many friends in the early days—the current moment feels as major a shift as 1996, when multi-drug cocktails came to market and people visibly on the verge of death recovered in ways that seemed miraculous. A friend quipped then that it was the first time in 15 years he could take his florist off speed-dial.

And yet: Major challenges remain, and in many ways the perception of AIDS as a chronic disease may make them harder to tackle.

As reported in a special section of Science two weeks ago, in the U.S., AIDS has become a disease of the poor, minorities, rural residents and disenfranchised groups—and as a result, has largely fallen off the mental radar screen of the rest of the country. A lengthy analysis published last December by Duke University’s Center for Health Policy and Inequalities Research made clear the new shape of the epidemic: The Southeast, with only 22 percent of the U.S. population, has 35 percent of new diagnoses, and nine of the 10 states with the highest rates of death from AIDS. And in a measure of how much AIDS has become a disease of poverty, the report found that the Southeast—one of the poorest and least healthy regions of the country — is home to 99.5 percent of people on waiting lists for AIDS drug-assistance programs.

In the rest of the world, particularly sub-Saharan Africa, AIDS has always been a disease of poverty and disenfranchisement. Its continued spread points like an arrow to the marginalization of racial and ethnic minorities, sex workers, and gay people in areas and cultures where homosexuality is frowned on, and especially to women’s inability to participate equally in societies. Globally, the group most at risk of infection is young women aged 15 to 24.

The many pieces of good news also may mask a crunch point: faltering investment. UNAIDS says that 2011 marked the first time low- and middle-income countries contributed more to the fight than big international funders, $8.6 billion versus $8.2 billion—a proportion shift made possible by the fact that international funding has not increased in four years. The U.S. remains by far the largest AIDS funder, having spent billions in the past decade via the President’s Emergency Plan for AIDS Relief and the public-private Global Fund for AIDS, Tuberculosis and Malaria. But as J. Stephen Morrison, director of the Global Health Policy Center at the Center for Strategic and International Studies, pointed out in the run-up to the AIDS conference, the economic crisis and looming election are undermining both the administration’s vision for global health action and its ability to fund bold moves—while the Eurozone crisis simultaneously imperils funding abroad.

As the International AIDS Conference opens, the scientific successes and social and economic stumbling blocks will be high on the agenda. But the epidemic has demonstrated time and again how real-world complexities can undermine expectations of progress. Outside its hotspots, HIV research, treatment and education are  particularly vulnerable to what longtime AIDS expert Kevin De Cock of the Centers for Disease Control and Prevention, calls “fatigue and forgetting.” Bringing the conference back to the country where AIDS was first recognized may offer a way to make the epidemic feel again like the emergency it continues to be.