michael specter--times--uganda trial of aids vaccine

the new york times urgency tempers ethics concerns in uganda trial of aids vaccine october 1, 1998 KAMPALA, Uganda--Raphael Nawiro got up extra early one steamy morning this summer. He walked a mile from his home, then took two long bus rides until he reached Uganda's principal medical complex, the aging, overburdened Old Mulago Hospital. He went directly to the office of Dr. Roy Mugerwa, who will run an AIDS vaccine trial that is about to begin here. "I want to enroll in the study," he told the secretary, eager to take part in a promising and ethically contentious experiment. "I want to help find a cure for what's killing us all." The secretary nodded gravely and told him where to go to fill out forms. "I can't promise a thing," she said. Nawiro, a schoolteacher, is under no illusions that the test of any vaccine will prevent him from becoming infected with HIV, the virus that causes AIDS. But at the age of 32 he has lost five members of his family to this plague, and he is weary of the endless death that has come to rule his country. "It's time to do something serious about this disease," he said quietly as he rushed off to work. "Isn't a vaccine really the only hope we have?" On this continent the answer to that dark question is a ringing, undeniable yes. People infected with HIV in rich countries now have access to drug combinations that extend their lives. But in Africa, where AIDS threatens to destroy an entire generation, there is no such reason for optimism. And unless somebody comes up with a vaccine, that is unlikely to change before millions more die. In the past, ethical guidelines have made clear that vaccines should be tested in developed countries--where health care is excellent-- before they are used in places without a safety net, like Uganda. With AIDS, for the first time, the international medical community has done away with that necessity. "It has to be this way," said Mugerwa, medical professor at Makerere University who is the principal investigator for the vaccine trial scheduled to begin in October. "Nobody is going to do it first anywhere else," he said, "and I don't blame them. We are the people with the problem. Why should Americans undertake risky research on themselves for a problem they don't really have? That would make them the guinea pigs. The risk belongs here, where the people are dying." In Uganda, a country struggling valiantly to cope with an epidemic that has infected 20 percent of its population, the questions surrounding the trial have become deafening. Who will take part in the first round, and what will happen if people become infected and sick after they have volunteered, given that Uganda spends about $6 per person annually on health care? Will they receive the best medical care that money can buy, as they would in America or France, two other countries that are testing AIDS vaccines? If they do, who will pay? If not, will they be treated like any other Africans--given aspirin, good wishes and no hope? What if, as is often the case with vaccines, this trial shows that it may not prevent an AIDS infection but it may make the disease less deadly? Should the test be stopped immediately so that the vaccine can be given to people right away, before scientists can find out the answers to how good the vaccine might ultimately be or how best to use it? Or should the test go on, with some people receiving a useless placebo, so that researchers can learn the full potential of any possible vaccine? And, although most scientific experts say there will be no useful AIDS vaccine for at least a decade, what will happen if that vaccine is eventually produced thanks to the help of the eager, fragile and desperate people of Uganda? What guarantee will there be, after helping to solve one of modern medicine's most frightening and complex problems, that any proven AIDS vaccine would be available here or in similar countries, where most basic medicines are too expensive to buy? Drug companies will want to recoup their enormous investments, and that means selling a vaccine to people who can pay for it. Few effective vaccines, even the one for hepatitis B, which was developed only after long testing in Senegal, have been made routinely available in Africa. They just cost too much. "Everybody is worried that we will use Africa, develop a vaccine there, say thanks and then take it back to Europe and America," said Dr. Peter Piot, the executive director of the United Nations AIDS Program, who has worked to focus more attention on the scope of the epidemic in the developing world. "I don't believe that will happen. But we are in a terrible position. The process is perilous. It is unfair. And it is filled with inequities--because the world is filled with inequities. "What is our choice? In Africa they need a vaccine. Should we just tell them we have too many ethical problems to help them find one?" A walk across the campus of the Old Mulago, this giant hospital complex that has served as ground zero in Africa's gruesome fight with AIDS, answers that question in about five minutes. There are no waiting rooms, but every landing on every floor overflows with sick people. Mothers in bright cotton robes sit quietly nursing their infants; old men wheeze in the stairwell. Hundreds of men and women sit in eerie silence, coughing and waiting for a number to be called. Some wait for days, sleeping when they can, eating if there is food. There is probably no hospital on earth--and possibly no country-- more besieged by the AIDS epidemic. Every pair of eyes seems to spell the word despair. So despite a rancorous debate in the West, where critics say Africans will be misused in any test here because the highest standards of care and of informed consent are impossible to attain, Uganda is about to begin its trial. And it is hard to find anybody in this country who thinks that's a bad idea. Forty healthy volunteers will be selected. Half will receive a placebo that would have no effect on an HIV infection. The other half will receive a vaccine into which some genes responsible for producing important HIV proteins, some building blocks of the virus, have been inserted. There will be no actual virus in the vaccine. It is an initial test and its purpose is to see whether it is safe and whether it it has any effect. If the vaccine stimulates the body's defenses--and the placebo does not--that will mean that the vaccine should undergo further tests on a larger group of people. There are different strains of HIV, known as clades, and the predominant strains from Africa are different from those usually seen in the West. Still, one of the critical questions about any vaccine is how widely it can be used, and the hope is that at least the basic building blocks of any vaccine that work on one strain would also work on the others. Because the vaccine may reduce the amount of HIV in people who have already become infected, it cannot really be tested broadly in the United States. Americans who are diagnosed with HIV now immediately start a drug treatment regimen aimed at cutting down the amount of the virus in their bloodstream. Anything less would be considered unethical. But if people in a vaccine trial are also on these new drugs, researchers would have no way to judge whether a vaccine is reducing the virus, or whether the medicine was doing it. Since people in Uganda cannot hope to afford such drug treatment, which can cost more than $15,000 a year, they are perfect subjects for such a vaccine test. "The question arises are we basically exporting our risky scientific research, from which we would benefit, to the third world?" said Thomas M. Murray, director of Case Western Reserve University's Center for Biomedical Ethics, speaking at a forum on the vaccine trials this year. Case Western, which for years has had a relationship with Makerere University Medical School, is one of the vaccine trial sponsors. "This is a far more morally complicated issue than critics of the research have ever made it out to be," Murray said. That's because it has become clear to many people that there are practical and cultural barriers to applying the same standards of ethics in America and Africa. In the United States, for example, informed consent is required for people who take part in drug tests. They need to know what the test will do, what the risks are and what the rewards are. In Africa, such consent is often given by husbands or doctors or tribal leaders and many health officials say the country simply doesn't have enough trained doctors to inform everyone about complicated programs like the AIDS vaccine trials. Informing a representative of a village would never be considered enough in America, but in Uganda who should decide what is enough? Most experts, in Africa and in the West, say that every participant always deserves to understand the risks and possibilities of trials. And most specialists believe that informed consent is not only possible in Africa, but essential if trials are to work. Still, there is simply not enough time or money in most cases to make certain that each potential risk or reward is understood. "Things seem so simple in a rich country," said Dr. Peter Mugyenyi, the director of Uganda's Joint Clinical Research Center, which will administer the AIDS vaccine trials here in conjunction with a consortium of groups that include the National Institutes of Health and Pasteur-Merieux, the French company that has developed the vaccine and will provide it for the study. "They sometimes talk about this in America like it's the Tuskegee experiment and we are simple, ignorant dupes," he said. In the Tuskegee experiment, one of medicine's most notorious abuses of research subjects, poor black men in Alabama were denied affordable, effective and widely available treatment for syphilis. They were not informed of their rights in the research or told what was happening to them. And they were allowed to get sick when penicillin could have cured them all. "It's terribly insulting to us and to the Western agencies and individuals who have worked with us," said Mugyenyi, who presides over a state-of-the-art research center staffed with highly trained scientists from Uganda, Europe and America. "Sure there are some questions that are hard to address, like how will these people be cared for if they become sick. But let's also look at the world and tell the truth. In the history of medicine the only things that have really worked to stop diseases in the third world have been vaccines. Drugs won't work for us. Prevention has obviously failed. "Education is almost impossible. Without a vaccine we are going to keep on losing and we are going to lose a lot.' More than a million people in Uganda have already died of AIDS. The country's leadership is easily the most open in Africa about the issue--the president and other leaders mention the disease in nearly every speech. It is only rare families where at least one member has not fallen ill. Mugerwa and his colleagues are aware that in the past, when vaccines have been developed in Africa, they disappear as soon as they become worth money. That is why Uganda decided to be in on every level of testing. "We are participating in the trials," he said, "not just with our citizens, but with our brains. We have demanded a role in the research and we have sent our best people abroad to help develop the drugs. When this vaccine becomes effective--in a year or 10 years or two generations--we want to be able to say that we have a central interest in this product and you owe us for it." That will help but it won't solve the problem. Representatives from Pasteur-Merieux have said that it is now impossible to guess how much a vaccine would cost since it does not yet exist. They have also said, repeatedly, that foundations, international relief agencies, pharmaceutical companies and governments will all have to band together to come up with enough money to buy vaccines for poor countries. The message is clear: First let's get a vaccine, then we will figure out how to get it to you. "If you are a student of history, it's not all that comforting to see how Africa has been treated in the past," said Dr. Edward Mbiddle, chief of Makerere University's Cancer Institute. "But you know what? If we are going to have a future, we can't afford to live in history."



			the new york times urgency tempers ethics concerns in uganda trial of aids vaccine october 1, 1998 KAMPALA, Uganda--Raphael Nawiro got up extra early one steamy morning this summer. He walked a mile from his home, then took two long bus rides until he reached Uganda's principal medical complex, the aging, overburdened Old Mulago Hospital. He went directly to the office of Dr. Roy Mugerwa, who will run an AIDS vaccine trial that is about to begin here. "I want to enroll in the study," he told the secretary, eager to take part in a promising and ethically contentious experiment. "I want to help find a cure for what's killing us all." The secretary nodded gravely and told him where to go to fill out forms. "I can't promise a thing," she said. Nawiro, a schoolteacher, is under no illusions that the test of any vaccine will prevent him from becoming infected with HIV, the virus that causes AIDS. But at the age of 32 he has lost five members of his family to this plague, and he is weary of the endless death that has come to rule his country. "It's time to do something serious about this disease," he said quietly as he rushed off to work. "Isn't a vaccine really the only hope we have?" On this continent the answer to that dark question is a ringing, undeniable yes. People infected with HIV in rich countries now have access to drug combinations that extend their lives. But in Africa, where AIDS threatens to destroy an entire generation, there is no such reason for optimism. And unless somebody comes up with a vaccine, that is unlikely to change before millions more die. In the past, ethical guidelines have made clear that vaccines should be tested in developed countries--where health care is excellent-- before they are used in places without a safety net, like Uganda. With AIDS, for the first time, the international medical community has done away with that necessity. "It has to be this way," said Mugerwa, medical professor at Makerere University who is the principal investigator for the vaccine trial scheduled to begin in October. "Nobody is going to do it first anywhere else," he said, "and I don't blame them. We are the people with the problem. Why should Americans undertake risky research on themselves for a problem they don't really have? That would make them the guinea pigs. The risk belongs here, where the people are dying." In Uganda, a country struggling valiantly to cope with an epidemic that has infected 20 percent of its population, the questions surrounding the trial have become deafening. Who will take part in the first round, and what will happen if people become infected and sick after they have volunteered, given that Uganda spends about $6 per person annually on health care? Will they receive the best medical care that money can buy, as they would in America or France, two other countries that are testing AIDS vaccines? If they do, who will pay? If not, will they be treated like any other Africans--given aspirin, good wishes and no hope? What if, as is often the case with vaccines, this trial shows that it may not prevent an AIDS infection but it may make the disease less deadly? Should the test be stopped immediately so that the vaccine can be given to people right away, before scientists can find out the answers to how good the vaccine might ultimately be or how best to use it? Or should the test go on, with some people receiving a useless placebo, so that researchers can learn the full potential of any possible vaccine? And, although most scientific experts say there will be no useful AIDS vaccine for at least a decade, what will happen if that vaccine is eventually produced thanks to the help of the eager, fragile and desperate people of Uganda? What guarantee will there be, after helping to solve one of modern medicine's most frightening and complex problems, that any proven AIDS vaccine would be available here or in similar countries, where most basic medicines are too expensive to buy? Drug companies will want to recoup their enormous investments, and that means selling a vaccine to people who can pay for it. Few effective vaccines, even the one for hepatitis B, which was developed only after long testing in Senegal, have been made routinely available in Africa. They just cost too much. "Everybody is worried that we will use Africa, develop a vaccine there, say thanks and then take it back to Europe and America," said Dr. Peter Piot, the executive director of the United Nations AIDS Program, who has worked to focus more attention on the scope of the epidemic in the developing world. "I don't believe that will happen. But we are in a terrible position. The process is perilous. It is unfair. And it is filled with inequities--because the world is filled with inequities. "What is our choice? In Africa they need a vaccine. Should we just tell them we have too many ethical problems to help them find one?" A walk across the campus of the Old Mulago, this giant hospital complex that has served as ground zero in Africa's gruesome fight with AIDS, answers that question in about five minutes. There are no waiting rooms, but every landing on every floor overflows with sick people. Mothers in bright cotton robes sit quietly nursing their infants; old men wheeze in the stairwell. Hundreds of men and women sit in eerie silence, coughing and waiting for a number to be called. Some wait for days, sleeping when they can, eating if there is food. There is probably no hospital on earth--and possibly no country-- more besieged by the AIDS epidemic. Every pair of eyes seems to spell the word despair. So despite a rancorous debate in the West, where critics say Africans will be misused in any test here because the highest standards of care and of informed consent are impossible to attain, Uganda is about to begin its trial. And it is hard to find anybody in this country who thinks that's a bad idea. Forty healthy volunteers will be selected. Half will receive a placebo that would have no effect on an HIV infection. The other half will receive a vaccine into which some genes responsible for producing important HIV proteins, some building blocks of the virus, have been inserted. There will be no actual virus in the vaccine. It is an initial test and its purpose is to see whether it is safe and whether it it has any effect. If the vaccine stimulates the body's defenses--and the placebo does not--that will mean that the vaccine should undergo further tests on a larger group of people. There are different strains of HIV, known as clades, and the predominant strains from Africa are different from those usually seen in the West. Still, one of the critical questions about any vaccine is how widely it can be used, and the hope is that at least the basic building blocks of any vaccine that work on one strain would also work on the others. Because the vaccine may reduce the amount of HIV in people who have already become infected, it cannot really be tested broadly in the United States. Americans who are diagnosed with HIV now immediately start a drug treatment regimen aimed at cutting down the amount of the virus in their bloodstream. Anything less would be considered unethical. But if people in a vaccine trial are also on these new drugs, researchers would have no way to judge whether a vaccine is reducing the virus, or whether the medicine was doing it. Since people in Uganda cannot hope to afford such drug treatment, which can cost more than $15,000 a year, they are perfect subjects for such a vaccine test. "The question arises are we basically exporting our risky scientific research, from which we would benefit, to the third world?" said Thomas M. Murray, director of Case Western Reserve University's Center for Biomedical Ethics, speaking at a forum on the vaccine trials this year. Case Western, which for years has had a relationship with Makerere University Medical School, is one of the vaccine trial sponsors. "This is a far more morally complicated issue than critics of the research have ever made it out to be," Murray said. That's because it has become clear to many people that there are practical and cultural barriers to applying the same standards of ethics in America and Africa. In the United States, for example, informed consent is required for people who take part in drug tests. They need to know what the test will do, what the risks are and what the rewards are. In Africa, such consent is often given by husbands or doctors or tribal leaders and many health officials say the country simply doesn't have enough trained doctors to inform everyone about complicated programs like the AIDS vaccine trials. Informing a representative of a village would never be considered enough in America, but in Uganda who should decide what is enough? Most experts, in Africa and in the West, say that every participant always deserves to understand the risks and possibilities of trials. And most specialists believe that informed consent is not only possible in Africa, but essential if trials are to work. Still, there is simply not enough time or money in most cases to make certain that each potential risk or reward is understood. "Things seem so simple in a rich country," said Dr. Peter Mugyenyi, the director of Uganda's Joint Clinical Research Center, which will administer the AIDS vaccine trials here in conjunction with a consortium of groups that include the National Institutes of Health and Pasteur-Merieux, the French company that has developed the vaccine and will provide it for the study. "They sometimes talk about this in America like it's the Tuskegee experiment and we are simple, ignorant dupes," he said. In the Tuskegee experiment, one of medicine's most notorious abuses of research subjects, poor black men in Alabama were denied affordable, effective and widely available treatment for syphilis. They were not informed of their rights in the research or told what was happening to them. And they were allowed to get sick when penicillin could have cured them all. "It's terribly insulting to us and to the Western agencies and individuals who have worked with us," said Mugyenyi, who presides over a state-of-the-art research center staffed with highly trained scientists from Uganda, Europe and America. "Sure there are some questions that are hard to address, like how will these people be cared for if they become sick. But let's also look at the world and tell the truth. In the history of medicine the only things that have really worked to stop diseases in the third world have been vaccines. Drugs won't work for us. Prevention has obviously failed. "Education is almost impossible. Without a vaccine we are going to keep on losing and we are going to lose a lot.' More than a million people in Uganda have already died of AIDS. The country's leadership is easily the most open in Africa about the issue--the president and other leaders mention the disease in nearly every speech. It is only rare families where at least one member has not fallen ill. Mugerwa and his colleagues are aware that in the past, when vaccines have been developed in Africa, they disappear as soon as they become worth money. That is why Uganda decided to be in on every level of testing. "We are participating in the trials," he said, "not just with our citizens, but with our brains. We have demanded a role in the research and we have sent our best people abroad to help develop the drugs. When this vaccine becomes effective--in a year or 10 years or two generations--we want to be able to say that we have a central interest in this product and you owe us for it." That will help but it won't solve the problem. Representatives from Pasteur-Merieux have said that it is now impossible to guess how much a vaccine would cost since it does not yet exist. They have also said, repeatedly, that foundations, international relief agencies, pharmaceutical companies and governments will all have to band together to come up with enough money to buy vaccines for poor countries. The message is clear: First let's get a vaccine, then we will figure out how to get it to you. "If you are a student of history, it's not all that comforting to see how Africa has been treated in the past," said Dr. Edward Mbiddle, chief of Makerere University's Cancer Institute. "But you know what? If we are going to have a future, we can't afford to live in history."

			Copyright (1998) The New York Times Company. Reprinted by Permission. New York Times material may not be used in any manner except for personal reference without the written permission of The New York Times Company.