Hiv: Sobering News From The Front

AIDS' unchecked spread returns the focus to prevention

Back in 1989, deadly HIV was spreading in the dark corners of America, striking drug users, the homeless, and others on the edges of society. So the National Institutes of Health began a study to find out if educational efforts such as those that had slowed HIV transmission among gay men could also work in inner cities. "The naysayers were legion," recalls David D. Celentano, an epidemiologist at the Johns Hopkins University School of Public Health and one of the study's principal investigators. "They said people won't change their sexual behavior."

The team forged ahead anyway, offering HIV prevention and counseling sessions to hundreds of men and women plucked from inner-city clinics. "These folks are all at very high risk for HIV, with multiple sex partners, partners with sexually transmitted diseases, and little condom use," says Celentano. The results, announced on June 18, show that the skeptics were wrong. The effort doubled condom use and cut high-risk sex--and gonorrhea in men--in half. That should curb new HIV infections, scientists say. "The study showed that interventions can make a difference even in the most disadvantaged populations," says Dr. Steven E. Hyman, director of the National Institute of Mental Health.

But this good news is sadly isolated and fragile. Against a global backdrop, the U.S. study is a poignant reminder of opportunities lost. At the 12th World AIDS Conference beginning on June 28 in Geneva, the world will hear, once again, how medicine's arsenal of drugs and governments' limited policies have barely made a dent in the spread of HIV. Tantalizing scientific discoveries about the virus' vulnerabilities will also be hot topics. "But we have to realize that this epidemic is not over," warns Dr. Helene Gayle, HIV prevention chief at the Centers for Disease Control.

REDIRECTION. Far from it. New data from the CDC show that, while deaths from AIDS slowed for the first time in 1996 and new infections have dropped from a peak of 100,000 annually, an estimated 40,000 Americans continue to become infected each year. Globally, the story is far grimmer. Some 40 million people around the world have been infected by the virus, which strikes an additional 16,000 every day. In nations such as Botswana and Zimbabwe, HIV lurks in up to 25% of youth and adults. And the vast majority of victims can't afford the current $1,000 per month for the new drugs--or even the lower prices that companies such as Glaxo Welcome PLC and Bristol-Myers Squibb Co. have agreed to charge in developing nations. What's desperately needed, argues Dr. Peter Piot, head of the U.N.'s AIDS effort, is a redirection of world resources to prevention efforts and treatments for the hardest-hit areas.

The continued spread of the epidemic is especially frustrating to public-health officials because they now know how to rein it in. In one of the world's few shining success stories, a massive educational effort combined with free condom distribution dramatically cut AIDS rates in Thailand--though recent budget cuts threaten the program. In a Zimbabwean project that Stanford University AIDS expert David A. Katzenstein will describe in Geneva, key factory workers were trained to educate their peers about AIDS. The effort cut infection rates by one-third. And in the U.S., studies by James G. Kahn of the University of California at San Francisco show that prevention strategies such as intensive counseling, needle exchanges, and treatment for drug addiction cost $5,000 to $40,000 per infection averted. That's a tremendous bargain compared to the costs of AIDS therapies, especially since addiction treatment also pays off big in decreased crime and higher employment.

Indeed, prevention alone could end the epidemic in the U.S. in 10 years, many experts believe. The problem is that Congress continues to block everything from needle exchanges and sex-education programs to condom ads. "We know what's effective, and we have the money," says Don C. Des Jarlais, AIDS-prevention expert at Beth Israel Medical Center. "We just don't have the political will." And neither does the rest of the world. In many countries, even talking about sex is taboo. So at Geneva, many scientists are insisting that the developed world must tackle the epidemic globally.

COMPLICATIONS. Geneva will offer updates on treatments and basic science. On this front, recent developments have tempered the euphoria of just two years ago, when new drug cocktails raised hopes for actual cures. On one hand, conference members will hear tantalizing anecdotal reports from Italy and France of patients who appear to be keeping the virus in check even after stopping treatment. Scientists are also finding evidence that holding viral levels down with drugs allows the immune system to bounce back, at least partly.

On the other hand, it's possible that the immune system may be permanently plagued by crucial gaps. "That's one of the most important questions facing us now," says researcher Dr. Michael M. Lederman at Case Western Reserve University. "Even after a year of therapy, the immune system is still not normal." The result may be new complications. One worrisome trend to be aired in Geneva is an unexpected rise in lung cancer.

What's more, the new drugs aren't holding viral levels down dramatically in up to half of patients. "My fear is that the treatment will fail in these people," says Lederman. In the meantime, such incomplete viral suppression could speed development of resistant viruses. Indeed, San Francisco General Hospital researchers have documented a case of transmission of an HIV strain capable of foiling all current drugs. And despite hype from pharmaceutical companies in Geneva, AIDS activists warn, progress in developing additional weapons has been disappointing. "One of the messages for people who have failed treatment is that they will have to hang on with piano wire and glue, because the near-term drug pipeline is pretty thin," says Martin Delaney, founding director of Project Inform, an AIDS treatment-and-advocacy group in San Francisco.

If today's AIDS patients can hold on long enough, however, basic science will find new ways to attack the virus. In mid-June papers published in Science and Nature, for example, a team led by Joseph G. Sodroski of Harvard University's Dana-Farber Cancer Institute and Wayne A. Hendrickson of Columbia University reported that it has puzzled out the three-dimensional shape of a protein called gp120, the "key" that HIV uses to unlock the door to cells. In an elaborate process, viral gp120 first attaches to a docking port, or receptor, on the target cell called CD4. Then, the combined gp120/CD4 complex binds to a second cell receptor. That, in turn, enables the virus to penetrate and infect the cell.

"STEALTH BOMBER." Sodroski and Hendrickson found that the virus is even more cunning than scientists had thought. In what Sodroski describes as a "stealth bomber" approach, HIV coats gp120 with sugar molecules to hide itself from the immune system. What's more, the protein has dangling loops that act like umbrellas to shield its most vulnerable parts from the body's defenses. Both features help explain how the virus can evade the immune system--and why vaccines based on the gp120 protein have failed.

But the scientists also found a potentially vulnerable spot. One of the sections that gp120 uses to bind to CD4 is a deep pocket in the protein. "It looks like a very attractive place to target with drugs," says Sodroski. A drug capable of filling the pocket might be able to prevent the virus from binding to and infecting cells. Moreover, better vaccines might be able to prod the immune system into making its own "smart bombs"--antibodies that could also home in on the vulnerable region. Sodroski is already working with SmithKline Beecham PLC on possible drug candidates. Another promising development comes from Durham (N.C.) startup Trimeris, where a peptide that blocks the next step in HIV's entry into cells is about to enter Phase II clinical trials.

Unfortunately, most drugs based on the new discoveries are years away. And an effective vaccine probably won't be ready for at least a decade. That's why prevention is so crucial. The Geneva meeting will offer plenty of evidence that science and public-health researchers already know how to fight the spread of the virus. But until governments get serious, the HIV clock will keep ticking at the relentless pace of 10 new infections every minute.

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