By Craig Timberg
Washington Post Foreign Service
Thursday, November 1, 2007
DURBAN, South Africa -- Few cases of AIDS have been as closely scrutinized as that of a former South African prostitute named Beauty. Scientists know when this 40-year-old woman became infected, how her body responded and what happened as her immune system collapsed.
But when the subject turns to how Beauty might have been protected from the AIDS virus in the first place, scientists have few good leads. This fall, pharmaceutical giant Merck & Co. halted study of one of the most promising possibilities, a genetically engineered vaccine being tested on four continents, because it simply did not work.
After this latest setback, and with billions of dollars spent on research over more than two decades, scientists say they do not know when -- if ever -- a vaccine will be available in the fight against one of the world's most devastating epidemics. The news has been nearly as bad for other technological solutions, including vaginal microbicides, one-a-day prevention pills and diaphragms.
"We are really groping in the dark," said Salim S. Abdool Karim, director of the Center for the AIDS Program of Research in South Africa, in the seaside city of Durban.
The recent string of failures has sent scientists back to the lab, where, by studying the first months of infection in subjects such as Beauty, they hope to unlock some of the most enduring mysteries of HIV, the virus that causes AIDS.
But as they do, pressure is building from other experts -- some epidemiologists, physicians and scientists -- to shift attention away from technological fixes. They favor devoting more of the world's $10 billion annual AIDS spending to proven, lower-tech strategies against HIV, such as circumcising men, promoting sexual monogamy and making birth control more easily available to infected women.
"It's criminal not to put money into the things that work, and the things that work are relatively inexpensive," said Malcolm Potts, a professor at the University of California at Berkeley and former head of Family Health International, a research group with extensive experience in fighting AIDS. "We're spending money in the wrong places."A Difficult Target
Scientists first identified AIDS in 1981. Despite more than 150 trials and steady flows of cash from the National Institutes of Health, the Bill and Melinda Gates Foundation and other major donors, there are few promising vaccine candidates, scientists say. The most anticipated, developed by NIH scientists, somewhat resembles the Merck vaccine and is due to enter trials soon.
HIV has proved a difficult target in part because it hijacks the immune system, turning the body's own defense mechanisms against it. Then the virus mutates so quickly that a tactic that works one week might be obsolete the next. Because nobody has ever been able to rid their body entirely of the virus, scientists say they do not know what a successful immune response would even look like -- making it harder to know how to provoke one with a vaccine.
Vaccines for polio, flu and measles are made from dead or weakened viruses. They generally do not cause disease, instead producing immunities that help vaccinated people battle the pathogens if encountered later at full strength.
Because scientists feared that even a dead or weakened version of the AIDS virus might cause a lethal infection, the Merck vaccine attempted to stimulate an immune response by altering a common, but much less dangerous, virus to include genetic elements of HIV. Though researchers did not expect the vaccine to prevent someone from contracting HIV, they thought it might prepare the immune system to battle a later infection, helping delay its progress to full-blown AIDS.
It didn't. The safety monitoring board for the trial called for it to be stopped Sept. 21 because the vaccine was ineffective.
Here in Durban, one of the most heavily infected cities in the world, researchers at Abdool Karim's center called each of their 53 vaccine trial participants with the grim news.
Bonga Mkhize, 24, who had received a shot in his upper arm over the past few months, said glumly, "I was expecting it to work."
Among a group of nearly 700 subjects worldwide who received two doses of the vaccine, 19 became infected with HIV, compared with 11 for a similarly sized group that received placebos. The finding alarmed some scientists and underscored the tricky ethics of using human subjects to test potential remedies for incurable diseases.
South African researchers last week began warning hundreds of volunteer test subjects that the vaccine might actually have increased their risk of contracting HIV.
Two trials for microbicides -- gels that women insert into their vaginas to prevent infections -- also ended when more women using the experimental substance became infected with HIV than those using placebos. Scientists theorize that vaginal irritation caused by these products may have made it easier, not harder, for the virus to infect women. A study of whether diaphragms might inhibit HIV found that they were also ineffective.
"It's been an appalling year for the biologists," said Francois Venter, president of the Southern African HIV Clinicians Society.Technology vs. Reality
A technology that has worked in highly controlled settings often fails in the context of actual sexual behavior.
Hospitals routinely use antiretroviral drugs, for example, to prevent infections in doctors and nurses stuck by HIV-infected needles. But when researchers asked healthy West African women to take such medicine every day, the difference in infection rates was so small that scientists could not determine whether the medicine worked.
Condoms, meanwhile, can block HIV but are not used routinely enough to reverse the widespread epidemics in sub-Saharan Africa.
Researchers have struggled to prove the effectiveness of other popular and heavily funded strategies. For example, many scientists believe that treating sexually transmitted infections should slow HIV by healing the ulcers that encourage infection. But five of six large studies so far have ended in failure.
Theories about the ability of HIV testing and counseling to encourage safer sexual behavior also remain unproved. In some studies, those who learned they had the virus reported altering their behavior; those who discovered they were not yet infected did not. But most studies have found that making HIV testing more available does not slow the spread of the virus, and a rigorous new one published recently in the publication JAIDS found the virus spread most swiftly among those with the greatest access to testing and counseling.
For a study of people at high risk for HIV, Beauty came each month to a clinic that had muffins and hot tea at the ready. Researchers tested her for HIV and gave her free condoms, extensive AIDS counseling and a modest stipend.
Yet when one of her regular customers -- a truck driver who paid about $35 per visit, four times the going rate -- insisted on not using condoms, she chose to risk contracting a lethal disease.
"I heard about it, but I didn't think it would happen," she said. "Your heart just tells you, you won't get it."
The unpredictable nature of human behavior helps explain the enduring allure of a vaccine. If one could be found, a single needle stick -- or maybe two or three -- would confer a degree of lifetime protection.
"Without a biomedical instrument to prevent HIV, basically the world will never be able to control HIV because people will never stop having sex," said Glenda Gray, the lead South African researcher on the Merck vaccine trial.New Push in Old Direction
As efforts to find a vaccine or other new technological tool against AIDS have faltered, the science behind several existing but lower-tech approaches has grown stronger.
Three studies in three African countries have found that circumcising men lowers their chance of contracting HIV by about 60 percent. And like a vaccine, circumcision offers lifelong protection.
Research shows that public campaigns encouraging monogamy also helped reduce the pace of new infections in Uganda, Kenya and perhaps Zimbabwe. In each nation, falling rates of multiple sexual relationships led to declines in HIV infection rates.
Numerous studies have demonstrated that making birth control easily available to women with HIV gives them the power to keep from having babies who might contract the virus. Providing antiretroviral drugs to pregnant women also limits transmission to babies, but the medicine now reaches only one in 10 African women who need it.
These approaches do not attract the money or attention enjoyed by potential technological fixes such as vaccines or microbicides.
A recent U.N. report calling for massive new spending on AIDS projected only about 1 percent of the money funding either circumcision or efforts to change sexual behavior. There was no line item for expanding access to contraception.
Potts, the Berkeley professor, said the time has come to shift priorities toward existing strategies, however imperfect.
"If we're defeated in one area, we pull our troops back and attack somewhere else. That's what we're failing to do," he said. "We need a military response, and we have a bureaucratic response."