Since it was first recognized 25 years ago, AIDS has killed more than 25 million people, making it one of the deadliest pandemics in human history.

Acquired Immune Deficiency Syndrome was once thought to be an incurable death sentence, labeled a "gay cancer" for the largely homosexual victims who contracted it in its early days. Now, HIV, the virus that causes AIDS, affects homosexuals and heterosexuals in nearly equal numbers, and though its affects can be managed, the disease continues to be one of the leading worldwide causes of death (see "AIDS At 25: Pandemic Has Spread Faster Than Awareness").

Nearly 40 million people around the world currently live with HIV, and despite a quarter-century of study, life-lengthening breakthrough treatments and continuing efforts to spread crucial messages about prevention, World AIDS Day (celebrated annually on December 1 since 1988) reminds us that the struggle is far from over. Every day, 11,000 people become infected by the disease worldwide — 40,000 annually in the United States alone — and a recent report predicted that within the next 25 years, AIDS will join heart disease and stroke as one of the top-three causes of death worldwide.

So, what has changed over the past 25 years?

Prevention

From the early days of the AIDS/HIV crisis, health care professionals consistently stressed the significance of prevention, from the use of condoms to the importance of IV drug users not sharing needles. Among the most prominent new prevention methods currently being investigated are pre-exposure prophylaxis and microbicides, both of which are in clinical trials around the world.

Of course, health professionals continue to encourage the diligent use of condoms, even as promising preventative developments such as PrEP emerge. PrEP works like this: HIV-negative people take antiretroviral drugs, such as Tenofovir, on a daily basis; the hypothesis is that treatment will already be in place if a person is exposed to the virus. Given the barriers women in some parts of the world face in negotiating condom use, one of the promises of PrEP is that it could put AIDS prevention in the hands of women and provide a safety net for all men and women at risk, according to the Centers for Disease Control and Prevention.

At the same time, scientists are testing microbicidal vaginal gels or creams that could be on the market as early as 2008. The gels are inserted into the vagina either daily or before intercourse. Some microbicides contain agents that stop the AIDS virus from adhering to and entering immune cells, while others inactivate viruses and bacteria.

"The most promise of the prevention tools is not the most immediate ... if you have microbicides, you're going to empower women to save their own lives and stop them from being infected," former President Bill Clinton said in August at the XVI International AIDS Conference. "A woman should never need her partner's permission to save her own life," added Microsoft founder Bill Gates at the same conference, where he and his wife said they would invest in microbicides through their Bill & Melinda Gates Foundation.

Treatment

In addition to the "cocktails" of drugs prescribed to many people with AIDS, current treatment methods used to treat the disease include post-exposure prophylaxis, a combination of anti-retroviral drugs administered two to 24 hours after exposure to HIV that lasts for 28 days. According to Frank Spinelli, director of the HIV program at Cabrini Medical Center in New York, the PEP method is proven to work, but should never be considered as a "morning-after pill" option because of its tricky timing — you can't always know when you get infected — and serious side effects.

Spinelli was also excited about a new once-a-day, one-pill regimen that combines three often-prescribed treatment drugs into one pill that he called "revolutionary" because two of the pills come from competing pharmaceutical companies. "These two pharmaceutical companies came together," he said. "And it's a great benefit for the patient, because not only is it the ease of taking it once a day, but also because they don't have to pay different co-pays."

Looking back on his six years working on the treatment of HIV, Spinelli said the difference between now and 25 years ago — when patients on 16-18 pills a day were suffering from serious side effects and facing almost certain death — is that the one-pill-a-day solution was almost inconceivable back then. "Now you're offering patients better treatment options, and tolerable drugs," he said of the single-pill solution called Atripla. "Now, if you give someone a diagnosis of HIV, it's not so much a death sentence anymore, because you can actually prolong their life into a natural, or prolonged existing life. At least they can treat it."

Even as other treatment methods are being developed, many people with AIDS continue to take a variety of drugs to manage the disease. For some, though, the idea of taking a dozen pills a day could soon be a thing of the past. Photography teacher Luna Luis Ortiz, 34, has been living with HIV for 20 years, and his 11-pill-a-day regimen has been reduced to three per day.

"A lot of the kids today don't know what it was like to be HIV-positive at a time where it was destroying the community, destroying people, breaking homes," Ortiz said. "And I would say to them, although we have the medications and you can live longer, it [is] still not glamorous or wonderful to have HIV. Basically, the HIV meds ... do sort of make you live longer, but of course your body is still changing and you are still breaking down." Remembering how more than 70 of his friends have died from AIDS since the 1980s, Ortiz added, "Imagine all of your friends gone and you are the only one left. It would be almost like a vampire, everybody around him is dying and you are the last one standing. I am living proof ... [that] it is not a death sentence. If you find out that you are HIV-positive, there is hope."

The search for the silver bullet everyone has been hoping for — an HIV vaccine — continues on five continents, with drug trials already under way, but no timetable yet for a finished product. Dr. Scott Hammer, one of the world's leading HIV/AIDS doctors and the head of infectious diseases at New York's Columbia University, said the search for a vaccine is elusive, but progress is being made in nations as diverse as Finland, Malawi, Cuba, Peru and India. The Project Advance-Step Study at Columbia has reached Phase II B of trials for a vaccine, where safety tests are being conducted to see if it can progress to Phase III, where it would test the actual efficacy on patients.

The study, which enrolls HIV-negative people, currently includes Legend Rivera, 24, and Sarah Leeper, 25, both of whom said they volunteered to be inoculated to make a contribution to helping people fight HIV. Rivera, a makeup artist, said he's not afraid if he tests a false positive during the study — the solution participants are injected with could increase their antibodies, one of the measurements used to detect HIV — and neither is Sarah, who is a pre-med student at Columbia.

Joseph Calabro, 37, found out he was HIV-positive in 1991 and was recently diagnosed with cancer, which was believed to be a result of his weakened immune system. Despite his belief that he's only got a year or two of life left, he said he's a living example of the life-sustaining abilities of the current AIDS drugs, as well as the importance of searching for new treatment and prevention options.

His message to young people, HIV-positive and negative, is a simple one. "The HIV-negative, I would definitely tell them to be a lot more careful," he said. "This has been a very big burden. And I've had it for quite a long time. And it is the only thing on my mind usually ... and they don't want that." As for the HIV-positive, Calabro said, "I would put my arm around them and tell them, 'Hey, we're in the same boat,' and, 'Take your meds.' I would say, 'Take care of yourself.' "