http://www.washingtonpost.com/wp-dyn/articles/A63781-2001Sep8.html
Imperfect
AIDS Vaccine Still Useful
Researchers Say 50% Effective Drug Could Change
Course of African Epidemic
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By David Brown
Washington Post Staff Writer
Sunday, September 9, 2001; Page A15
A poor AIDS vaccine would have to be used by nearly an entire population to
have any benefit. However, even with less-than-complete coverage, such a vaccine
could prove useful if already-infected people had access to antiviral drugs,
which reduce a person's likelihood of transmitting the virus to someone else.
On the other hand, if people were to greet the arrival of a modestly
effective vaccine by increasing their risky sexual behavior even a little, all
benefit would disappear.
"We don't need a perfect vaccine to have a public health impact. Even
one that is only moderately protective could control the epidemic," said
Ronald H. Gray, of the Bloomberg School of Public Health at Johns Hopkins
University, who created a mathematical model that tested the effects an AIDS
vaccine would have on Uganda, one of the worst-hit nations in Africa.
In the Rakai district of Uganda, about one in every 900 acts of heterosexual
intercourse results in a new infection with human immunodeficiency virus (HIV).
As in the rest of Africa, this is the main mode of virus transmission.
Each infected person in Rakai infects an average of 1.34 other people before
he or she dies. That is called the "reproductive number" of the
epidemic, and if it can be reduced to less than 1, disease transmission will
abate and, theoretically at least, eventually burn out.
Gray and his colleagues calculated that a 50 percent effective vaccine would
have to be taken by everyone in Rakai to tip the reproductive number below 1. A
75 percent effective vaccine used by half the population would do the same
thing.
Even a 25 percent effective vaccine used by three-quarters of the population
would drive the number below 1 if already-infected people received antiviral
treatment at the stage of disease recommended by guidelines from the Department
of Health and Human Services, Gray calculated.
Such treatment does not exist in Africa now. But with deeply cut drug prices
and the United Nations' recent decision to create a global fund to buy AIDS
drugs for the developing world, the possibility is not entirely out of the
question.
In Rakai, 25 percent of men, and 4 percent of women, have extramarital
intercourse each year. If that behavior doubled after the widespread
introduction of a 50 percent effective vaccine, the epidemic would actually
worsen.
"It will completely wipe out the benefit of the vaccine," said
Gray, who produced the model with the help of researchers at Columbia
University and Uganda's Makerere University.
There are two large-scale AIDS vaccine trials underway. The bigger and
longer running involves 5,100 gay men and 300 women recruited at 61 sites in
the United States, Canada and the Netherlands.
All are at high risk of acquiring HIV because of their sexual practices.
Two-thirds received a vaccine containing a protein called gp120 taken from
HIV's envelope, or outer covering. The remaining one-third were injected with a
placebo.
The researchers conducting the trial estimate that about 1.5 percent of
participants will become infected each year (assuming those getting the vaccine
are not protected by it). The Food and Drug Administration has suggested it
would consider approving an AIDS vaccine if a trial shows with a high degree of
certainty that the substance reduces the rate of HIV infection by at least 30
percent.
The trial, which is costing about $200 million, is scheduled to last three
years, ending in late 2002. However, an independent monitoring panel will
secretly review the data in November to determine whether the vaccine is
unusually effective. If it is -- and it would have to cut infections by more
than 60 percent -- the study would be stopped ahead of schedule. People who
received the placebo would then be offered the vaccine.
"I think it's a high hurdle to achieve," said Donald P. Francis,
president of VaxGen, the California biotechnology company that makes the
vaccine. "I would be surprised if it were stopped."
Interviews with people in the trial suggest for the most part that possible
access to a vaccine is not causing an increase in risky behavior. At the start
of the study, 60 percent of the gay men reported having unprotected anal sex in
the previous six months. One year into the trial, 46 percent reported they had.
The women, many of whom are users of crack cocaine who have traded sex for
drugs, also reported a lower rate of unprotected intercourse a year into the
study. Curiously, though, the women who felt strongly they had received placebo
injections reported higher rates of risky behavior than at the start.
"They have difficulty understanding the concept of placebo," said
Bradford Bartholow, one of the researchers. "Many women believe the
placebo is the vaccine."
The designers of the second trial, which is testing a vaccine in 2,500 drug
users in Bangkok are addressing that problem in a highly unusual way.
As part of the process of giving "informed consent," volunteers
must take a test to determine whether they understand the purposes, procedures,
risks and benefits of the vaccine trial. Each person must take the test twice,
more than 24 hours apart, and pass it with an 80 percent score. Furthermore, a
person must correctly answer all of a core group of questions the researchers
believe are essential for understanding what a volunteer is getting into.
That trial, which is also testing the VaxGen gp120 vaccine, will run about
two more years.
An issue in vaccine trials, especially those in developing countries, is how
to treat people who become HIV-infected during the study.
In the Bangkok trial (in which about 300 people are expected to acquire the
virus, assuming the vaccine doesn't work), VaxGen bought local health insurance
policies for all the participants, at a cost of about $2.50 a person. People
who become infected will be treated under the national guidelines set by the
Thai government's health ministry. Starting next month, those guidelines ensure
that all HIV-infected people will get three-drug combination therapy (without a
drug from the expensive protease-inhibitor family).
The U.S. Army hopes to start another AIDS vaccine trial in Thailand next
year, which would enroll about 16,000 non-drug users. The Defense Department
will "support . . . drug availability" for people who become infected
in that study, Col. Deborah L. Birx said.
There is no guarantee that every person in a developing country who becomes
infected during a vaccine trial will receive triple-drug therapy for life
provided by a study's sponsors. But UNAIDS, the AIDS organization run by the
United Nations and World Bank, has said it expects that people who become
infected during vaccine trials will be provided medical care that is at least
somewhat better than what is available for the general population of the
country where the study is held. Precisely what that consists of will be
negotiated by the parties involved.
Malegapuru Makgoba, a physician who heads South Africa's Medical Research
Council (the equivalent of this country's National Institutes of Health), said
he is confident that equitable arrangements can be made. Early plans are
underway for a vaccine trial in his country sponsored, in part, by those two
research entities.
"All the institutions have reputations to protect. They have integrity
to deal with. Their necks are on the line," he said.
© 2001
The Washington Post Company
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