AIDS

The Beginning of the End?


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For nearly 15 years, “Mike” has been living with a would-be assailant. His is a formidable foe, one authorities variously describe as cunning, relentless, devious and deadly—a stealth invader designed by nature itself to finally dispatch him. But through all those years, this natural-born killer has been kept at bay.

There are any number of labels one might hang on Mike: veteran (he received an honorable discharge from the United States Army in 1968), senior citizen (he’s 63), self-provider (Mike doesn’t have a partner, lives alone, fends for himself), gay (“I was in the Army before ‘Don’t ask, don’t tell,’” he says. “They didn’t ask. I didn’t tell”). And the one label that stings the most: HIV-positive. Mike was diagnosed with the human immunodeficiency virus (HIV) that causes AIDS—the acquired immune deficiency syndrome—in November 1995.

“At the time, I was told I had two months to live,” Mike says, his hazel eyes glinting in the afternoon sun. He looks younger than his years. A thick crop of salt-and-pepper hair frames his lightly tanned face. He greets his visitor with a ready smile and seemingly boundless energy. Clearly, Mike does not project the stereotypical image of those stricken with HIV. But his healthy appearance belies a host of medical problems, some of which are born of, or are byproducts of, the medications he takes to fend off the virus that lurks always, somewhere in his body.

For as long as he has been diagnosed, Mike has been taking protease inhibitors, powerful medications used to treat infection by a number of viruses, including HIV. He has survived quadruple bypass surgery. And he suffers from diabetes and nerve damage that causes tingling in his hands and feet, common side effects of protease inhibitors.

“But the drugs are keeping me alive,” he says. “It’s a tradeoff.”

Mike is one of 6,000 people who access services offered by Being Alive, one of the first organizations in San Diego County to provide support for people living with HIV/AIDS. Being Alive was launched in 1989, when a positive diagnosis was generally viewed by the public—and the media—as a death sentence.

Shannon Wagner, executive director of Being Alive, has been with the organization since 2001. In the intervening years, she has seen a gradual evolution in public attitudes toward people with HIV/AIDS.

“But there’s still a stigma attached to HIV and the people who are HIV-positive,” Wagner says, “although young people seem far less judgmental.”

It is without question a commanding stigma, as powerful as Hester Prynne’s scarlet letter, and for many, equally laced with concepts of sin and guilt—one of the chief reasons Mike opted not to use his real name for this story.

When he first learned he was HIV-positive, Mike says, it was a shock. Today, nearly 15 years later, he is determined, even sanguine.

“I’m not sure that I’ll be around to see the end of AIDS,” he says. “I’d love to, though. I’d love to be able to see the other side of the epidemic, to see the world look back on AIDS as something out of the dark past.”

The Long, Long Road

Not long after the virus that causes AIDS was identified, Margaret Heckler, then U.S. Secretary of Health and Human Services, announced at a news conference that the discovery of the human immunodeficiency virus would enable scientists to develop a vaccine to prevent AIDS. “We hope to have such a vaccine ready for testing in approximately two years,” she said, beaming. That was in 1984.

After three decades of frustration and false starts in an urgent quest to find an effective vaccine against HIV, science appears to be entering what researchers are calling a “renaissance” in their fight against AIDS. Their target is a pandemic that has claimed tens of millions of lives on a global scale since it first emerged in the early 1980s. Scientists with The Scripps Research Institute and the International AIDS Vaccine Initiative (IAVI) have discovered two powerful new antibodies capable of neutralizing scores of different HIV strains. Their discovery could prove to be the basis for an effective vaccine against the disease, which kills an estimated 2 million people every year.

Dennis Burton, a professor of immunology and microbial science at The Scripps Research Institute, is among a growing chorus of scientists and researchers voicing optimism in their fight against HIV/AIDS.

“All of our research seems to be pointing in the right direction,” says Burton, who led the Scripps study. “In fact, I’m convinced we’ll see a vaccine for HIV within our lifetime.”

These new antibodies are not the first so-called broadly neutralizing antibodies, or bNAbs, to be isolated from HIV-positive subjects. Scientists previously had pinpointed four bNAbs. But these two new super-antibodies are the first to be discovered in a decade, and they appear to be at least 10 times more effective in incapacitating HIV than earlier versions.

“They are the best clues we’ve ever had in terms of understanding what isolates and destabilizes HIV,” says Wayne Koff, Ph.D., senior vice president of research and development with the IAVI in New York City. “Collectively, researchers made more advances in 2009 than we’d seen in a very long time. I really believe this is a renaissance in the development of an HIV vaccine.”

A similar strain of optimism runs through an assessment by Dr. Anthony Fauci, director of the Maryland-based National Institute of Allergy and Infectious Diseases. “Several years ago, we weren’t so sure, but now I’m convinced we will have a vaccine,” he says.

The discovery of the two new antibodies hinged on global collaboration across continents, governments and scientific disciplines. The Scripps Research Institute, a nonprofit organization, is recognized internationally for its discoveries in immunology, biology and infectious diseases. The IAVI, also a nonprofit, operates in 24 countries around the world and was founded in part with the support of the governments of Canada, Denmark, India, Sweden, the United Kingdom and the United States, among others.

“No one country, no one government, no one research team is going to find an HIV vaccine,” says Mitchell Warren, executive director of the New York–based AIDS Vaccine Advocacy Coalition, an international group focused on the development and delivery of AIDS vaccines. “We’re seeing unprecedented collaboration in this pursuit. Clearly, we’re in a better place today than we’ve ever been in terms of finding an HIV vaccine.”

Collaboration is evident in the makeup of the Scripps study. In addition to Scripps and the IAVI, the research team includes two Seattle and San Francisco–based biotech firms.

The findings of the Scripps study, published late last year in the journal Science, provide hope for an eventual vaccine because the new antibodies the research team discovered are capable of neutralizing many strains of HIV.

“These antibodies are telling us something,” Burton says. “They’re telling us that we’re shooting for an achievable aim. They exist in infected people. But if we could induce them before a person became infected, then there would be a very good chance that they would never get infected. In other words, they’re telling us that a vaccine is possible.”

In the study, doctors in Thailand, Australia, the United Kingdom, the United States and Africa collected blood samples from 1,800 people who had been infected with HIV for at least three years without developing symptoms of the disease. Those subjects were the most likely to create antibodies in their blood­streams that prevented HIV from entering their blood cells. When all 1,800 samples were screened, the results pointed to two antibodies (the new bNAbs) that were drawn from one subject in Africa, epicenter of the pandemic.

“We were looking at 162 HIV viruses—a snapshot of what’s circulating out there in the world, and these two antibodies neutralized about 130 of them,” Burton says. “For one single antibody to stop almost 80 percent of the viruses is extraordinary. It’s terrific news.”

Biology 101 Revisited

To grasp the emerging wave of research coursing through scientific circles worldwide in the fight against HIV, most of us who are not scientists might want to dust off the yellowed pages of a Biology 101 text for a mercifully brief refresher.

Remember the last time you were laid low by a virus? Maybe you were sick with the flu for a few days or weeks. You felt miserable because a pathogen—a foreign agent, if you will—had invaded your body. Your natural immune system, charged with keeping you healthy and preventing infection, quickly kicked into gear. The immune system’s goal was to identify the agent (a flu virus, for example), which, if left un­checked, could seriously damage its host—you. Once the virus was identified, the immune system dispatched its foot soldiers, special cells known as T-cells, to attack and destroy it.

Even without a vaccine, your body can mount an effective response to many pathogens. Following a natural infection, you develop an immunity that protects you if you are ever exposed again to that same pathogen.

Vaccines, such as those that combat measles and mumps, are able to fool your body into thinking that it is infected. The vaccine usually contains a weakened pathogen or a component of the pathogen that won’t cause disease. Your immune system then produces antibodies, which latch onto the pathogen and prevent it from infecting healthy cells. Eventually, they also target the pathogen for destruction by T-cells. Broadly neutralizing antibodies are capable of blocking viruses from multiple strains, rendering them unable to infect their target cells.

HIV: A Shifting Target

There are a number of reasons why HIV has eluded the designers of vaccines; chief among them is the virus’ tremendous capacity for mutation. Scientists say HIV is by far the most mutable virus they’ve ever encountered. There are a number of different subtypes of the virus circulating in separate regions of the world, and there are variations within those subtypes. Beyond that, the virus mutates at a furious pace within each infected person.

“The problem with HIV is that even one single person who is infected can harbor literally thousands of slightly different variations of the virus,” Burton says. “You’re not trying to vaccinate against one virus but a whole swarm of viruses.”

And since no one has naturally cleared an HIV infection, researchers don’t know which immune response can control the virus.

“For reasons we’re just beginning to understand, the human body doesn’t mount a natural response to HIV,” Fauci says. “Of the tens of millions of people who have been infected with the virus, not a single one of them has been able to completely eradicate it from their body.”

Hold the Champagne

Researchers temper their excitement over recent breakthroughs in their battle against HIV/AIDS with a heady dose of reality.

 “In all of science, no matter what the breakthrough, there are no ‘Aha!’ moments in the lab,” Warren says. “Major breakthroughs are the result of building one discovery on another.

“It’s not time to pop the champagne cork and say we’ve found a vaccine or a cure,” he cautions. “But it is time to celebrate the possible, something we haven’t been able to do in 20-plus years.” 

Snapshots of a Pandemic

  • Every day, 7,500 people worldwide are infected with HIV.
  • Each year, about 40,000 new HIV infections occur in the United States. In 2007, there were an estimated 14,560 AIDS-related deaths in the United States.
  • Globally, more than 33 million people are infected with HIV, including 2 million children.
  • In 2008, more than 2 million people died of AIDS-related causes. During the same year, 2.7 million new cases of HIV were reported.
  • About 430,000 children were born with HIV in 2008.
  • Sub-Saharan Africa is home to 67 percent of all people living with HIV. The AIDS epidemic has orphaned more than 15 million children in the region.
  • By the end of 2007, women accounted for half of all adults living with HIV (59 per­cent in sub-Saharan Africa).
  • More than 25 million people have died of AIDS since the epidemic emerged in the early 1980s.

Sources: Centers for Disease Control and Prevention, international AIDS charity AVERT, the World Health Organization, the United Nations agency UNAIDS and the Global AIDS Alliance.

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