New York Times News Service

c. 1998 New York Times Company

Thursday, October 1, 1998

AIDS Vaccine Trial In Uganda Marked By Controversy And Hope

By MICHAEL SPECTER

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."

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."