Vigilance and setbacks in the AIDS fight
SELDOM HAS the prospect of containing the AIDS epidemic looked so discouraging.
The best strategies for preventing the spread of the disease have always been the creation of a preventive vaccine or a gel able to kill the AIDS virus when applied before sexual intercourse.
These measures are far more reliable than the important but limited public health practices currently available - trying to change human behavior in terms of condom-protected sexual pursuits and/or abstinence, or trying to prevent exposure to contaminated blood via needles used by drug abusers.
As matters stand, the extraordinarily wily HIV virus, which causes AIDS, infects more than 33 million people worldwide, according to the United Nations.
Nearly a quarter-century ago, Margaret Heckler, the secretary of Health and Human Services, predicted a vaccine against AIDS would be ready for testing within two years. Now most AIDS specialists predict that it will take at least 20 years before we have one that works.
In September, human trials using the most promising anti-HIV vaccine, the
Hopes had been high that this vaccine might largely, if not wholly, prevent the transmission of new HIV infections. Ideally, such a vaccine would also help as a treatment for patients already infected by lowering the quantity of internal virus production.
The vaccine used a common cold virus (adenovirus 5), weakened so as not to cause any respiratory illness, as a vector for the HIV components. Attached to this respiratory virus were harmless segments (three key genes) of HIV known to be ones that would prompt the immune system to single them out as the targets of a full-scale attack against them. It was reasoned that the immune system would produce enough anti-HIV responses to protect a person against exposure to HIV. The Merck model vaccine had worked that way in monkeys, but it didn't work in humans.
Not only was the HIV-specific immune response insufficient to protect people, there were also worrisome suggestions that the vaccine might enhance the likelihood of HIV infection following exposure in real life.
No one is certain how this vaccine might inadvertently increase the risk of HIV infection. Some specialists speculate that since most of us carry biologic "memories" of adenovirus 5, its use as a vector for HIV genes might have inadvertently stimulated an outpouring of the wrong immune response cells, some of which were then more susceptible to real HIV shortly after vaccination.
Cancellation of the Merck vaccine trials was particularly disheartening within the AIDS research community because it will hold up trials with the next promising vaccine in line for testing, a model from the National Institutes of Health model that somewhat resembles Merck's.
This was not the first AIDS vaccine to fall by the wayside. Earlier this decade, others had failed whose designs were more closely patterned after the prevailing vaccines against such diseases as polio and measles. The Merck vaccine design was revolutionary by comparison.
Other promising anti-AIDS agents also have failed in human trials. Microbicides - gels to thwart the AIDS virus by harming or killing it - were first seen some 10 years ago as likely candidates to prevent the spread of AIDS on a large scale.
Results from trials with the first HIV microbicide, nonoxynol 9, were reported five years ago. This year, results from the second such product, Ushercell, came in. Both not only failed to protect against HIV transmission during sexual intercourse, but also seemed to increase the risk for HIV infection.
Fortunately, progress with drugs to treat and control AIDS disease has been substantial. Through combinations of these medicines, the majority of patients in such economically advantaged nations as the United States live out extended and productive lives. For them, AIDS is no longer the death sentence it once was.
Such success with anti-AIDS drugs, however, is still more the exception than the norm across the world. Only 10 percent of the tens of millions living with HIV today have access to effective drugs. Through long-term, multibillion-dollar programs like President Bush's Emergency Plan for AIDS Relief, the Global Fund, and the Clinton and the Bill & Melinda Gates foundations, millions more AIDS patients in developing countries will receive treatment next year and beyond.
Today, more is known about the AIDS virus than any other in medical history, even though it changes its structure billions of times in each infected person - far more than any other virus.
Still, AIDS has become the leading cause of death in all of southern Africa and in many populations of young adults worldwide. While success with treatment is now reality, prevention of AIDS through vaccines and microbicides will follow as long as we remain committed.
Max Essex is professor of health sciences and chairman of the Harvard School of Public Health AIDS Initiative. Loretta McLaughlin is former Boston Globe editorial page editor and a senior fellow at the Harvard AIDS Initiative.
