Coping with HIV’s Ethical Dilemmas
By: Tim Beardsley
From: Scientific American, July 1998
J. Geffen
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1.
AIDS has challenged ethical precepts from the earliest days of the pandemic,
and it continues to pose agonizing dilemmas in countries rich and poor. AIDS patients
and others infected with HIV, the AIDS virus, face discrimination of various sorts the
world over, and the high cost and long-term nature of treatment aggravate quandaries
that occur to a lesser degree in other serious diseases. Major battles revolve, in
particular, around ensuring access to therapies and testing new ones in an ethical
manner.
2.
Fear of contagion has sometimes led to discrimination against HIV-infected
people not only by the public but also by medical personnel, and some related legal
struggles from the early days of the epidemic continue. This summer the U.S.
Supreme Court should rule on an appeal from a dentist who refused to treat an HIVinfected woman in his office. She successfully sued, alleging discrimination under the
Americans with Disabilities Act. The case could change the legal interpretation of
disability.
3.
Yet discrimination is only one of the ethical issues that HIV has raised for
medical professionals and society. The best available therapy, which usually
combines three drugs that suppress viral replication, must be continued indefinitely
and costs more than $10,000 a year. Although states have instituted assistance
programs to provide anti-HIV drugs to those who would otherwise be unable to get
them, the funds are limited, and so the poor have less access than those with good
insurance policies.
4.
Money is not the only obstacle to equitable care. Triple therapy involves taking
a minimum of eight HIV-fighting pills (and frequently many more) a day on an often
complex schedule, in addition to any other medicines the individual might need.
Patients who fail to follow the directions risk encouraging the proliferation of drugresistant virus in the body, making subsequent treatment more difficult and increasing
the risk that the patient will pass resistant virus to others. Physicians therefore
sometimes advise against triple therapy for patients who seem unlikely to adhere to
the regimen dutifully. “Compromises are made,” says Douglas D. Richman of the
University of California at San Diego School of Medicine, an expert on drug
resistance in HIV.
5.
Advances in therapy in the past two years have also raised ethical issues that are
now affecting the conduct of clinical trials. Physicians have learned that no anti-HIV
drug works for long by itself and that solo use of a drug promotes resistance to it.
Therefore, biomedical ethicists agree it is no longer appropriate to conduct long-term
Coping with HIV’s Ethical Dilemmas / 2
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trials of any single drug in HIV-infected patients in the U.S. The need to maintain
high ethical standards has thus greatly increased the complexity – and cost – of new
trials.
6.
Ethical agreement has been impossible to find in a bitter argument over the
propriety of rich countries sponsoring in poor countries studies that would be
unethical at home. The controversy erupted in 1997, when Peter Lurie and Sidney M.
Wolfe of Public Citizen’s Health Research Group insisted that certain research being
sponsored in developing countries by the Centers for Disease Control and Prevention
and the National Institutes of Health, as well as the Joint United Nations Program on
HIV/AIDS, was unethical and exploitative. The studies were aimed at learning
whether a short course of the drug zidovudine (AZT) or various other inexpensive
therapies could prevent the transmission of HIV from infected women to their babies
in several countries in Africa and Asia.
7.
Lurie and Wolfe objected to the studies because scientists knew even before
they started that zidovudine reduces transmission of HIV by about two thirds if the
drug is administered in a regimen known as ACTG 076 (so called because a trial with
this designation proved the regimen’s value). In this protocol the drug is administered
during the last 26 weeks of pregnancy, during delivery (by intravenous drip) and to
the baby for six weeks after birth. But the regimen, which costs about $800, is too
expensive for wide use in developing countries.
8.
The disputed studies sought to determine whether a much less expensive course
of zidovudine or other medication, given only during the last three to four weeks of
pregnancy and costing no more than a tenth as much as the ACTG 076 protocol, could
still achieve a worthwhile reduction in HIV transmission. Lurie and Wolfe objected to
the decision to place some mothers in a control group in which they received only
fake medicine that was of no value to their babies. They argued that instead of
comparing a short course of medication with a placebo, the investigators should have
compared the short course with the full ACTG 076 protocol to see how closely the
two were equivalent.
9.
Defenders of the trials, notably Harold E. Varmus, director of the NIH, and U.S.
Surgeon General David Satcher, argued that by including placebos investigators could
learn more – and more quickly – about the value of inexpensive treatments in
reducing transmission. The placebos were necessary to learn the baseline transmission
rates without treatment, because these rates vary in different parts of the world, for
reasons that are largely obscure.
10. Moreover, the defenders asserted, placebos would help identify any important
toxicity of the drugs studies – not an insignificant concern, as anemia, one of the
known side effects of zidovudine, is much more common in undernourished populations than in the U.S. The trials did no harm, Varmus and others pointed out, because
the placebo – no treatment – was the standard of care in the countries under study.
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“Research does not create an entitlement,” concurs Robert J. Levine of Yale
University.
11. Lurie and Wolfe and their supporters were not satisfied. No foreseeable toxicity
from zidovudine or other therapy could counterbalance the babies’ lives that might
have been saved by using the ACTG 076 protocol in the comparisons, they
maintained. Other critics believe certain participants in the trials may not have given
true informed consent.
12. Wendy K. Mariner of Boston University holds that trials such as the disputed
ones can be ethical only if there is a plan at the outset to make the treatment available
to the local population if it proves to be effective. In fact, there was no plan to provide
it at the time the studies got under way, Mariner says. Yohana J.S. Mashalla, vice
president of the Medical Association of Tanzania, faults the studies as exploitative,
for setting out to demonstrate in developing countries the value of a therapy that
might then be adopted in developed ones.
13. Right or wrong, one of the studies sponsored by the CDC, which took place in
Thailand, did show in February that a three- to-four-week course of zidovudine
reduced transmission significantly – though not as much as the ACTG 076 protocol.
Over the following weeks, agencies started supplying the short course of the drug to
women in studies around the world who had previously received only a placebo. The
manufacturer of zidovudine, Glaxo Wellcome, then announced that it would cut prices
of the drug for developing countries. But as of May, it was unclear how many women
who needed the medicine would gain access to it.
14. The question of when to use placebos represents a “genuine conflict” between
getting the fastest answers to critical questions and the interests of today’s patients,
says bioethicist Arthur L. Caplan of the University of Pennsylvania. But in his
opinion, as a researcher “you owe something to your subjects – you owe them the best
options.”
15. One “underused tool” that could provide patients with better options is wider
application of innovative statistical designs, according to Christopher R. Palmer of the
University of Cambridge. Mathematically rigorous data-dependent designs for studies
can, in some cases, provide firm information on the effectiveness of a therapy while
exposing fewer patients to suboptimal treatment than a conventional trial would.
During a data-dependent study, the health of the participants is continually analyzed.
The accumulating evidence about the different treatments modifies the odds used to
select which therapy the next participant will receive.
16. Data-dependent designs are as yet little used, partly because many medical
statisticians are unfamiliar with the specialized math involved. But they are often
ethically attractive for late-stage studies on serious diseases, Palmer notes.
17. The dilemmas of research on HIV will become especially acute when candidate
HIV vaccines become available for large-scale trials. Because triple therapy is the
standard of care in the industrial nations, some, including Lawrence O. Gostin, law
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editor of the Journal of the American Medical Association, say researchers have an
obligation to provide it to all participants in vaccine trials who become infected.
Vaccine manufacturers, though, may well blanch at the cost of supplying triple
therapy even temporarily for thousands of enrollees.
18. HIV will continue to tax society’s conscience until inexpensive, highly effective
therapies and vaccines are available for all. And that day can come only through more
research. Meanwhile the desperate souls who sign up for a trial of a new drug or
vaccine must do so knowing they are taking a risk – but perhaps a reasonable one that
may benefit humanity’s collective future.
Coping with HIV’s Ethical Dilemmas / 5
Answer in your own words in English, unless otherwise indicated.
Answer the question below in English.
1.
What does the title itself suggest?
Answer : ____________________________________________________________
2.
Answer the question below in English.
What seems to make the position of HIV-infected people – paragraph 2 – all the
more difficult?
Answer : ____________________________________________________________
3.
4.
Answer the question below in English.
Discuss the connection – paragraph 3 – between poverty and an HIV patient’s
immediate chances of survival.
Answer : ____________________________________________________________
Why is lack of self discipline and orderliness liable to prove destructive or even
fatal – paragraph 4 – in the treatment of the HIV infected?
Answer : ____________________________________________________________
Answer the question below in Hebrew.
5.
Discuss the arguments presented for and against AIDS research – paragraphs 68 – as conducted by Western medical authorities among HIV infected patients in
poor Third World countries; what makes it so ethically problematic?
Answer : ____________________________________________________________
Coping with HIV’s Ethical Dilemmas / 6
Choose the best answer.
6.
Accepting Robert J. Levine’s statement – paragraph 10 – would suggest that
those conducting the experiments are morally
a. deficient.
b. commendable.
c. guiltless.
d. reprehensible.
Answer the question below in Hebrew.
7.
Explain the essence of Levine’s statement.
Answer : ____________________________________________________________
8.
9.
10.
Answer the question below in Hebrew.
How do some researchers – paragraphs 8-10 – attempt to justify the use of
placebos in AIDS research in poor countries?
Answer : ____________________________________________________________
Answer the question below in English.
What are the preconditions for conducting AIDS trials as laid down by Wendy
K. Mariner – paragraph 12?
Answer : ____________________________________________________________
Answer the question below in English.
What is likely to hold up the large scale experiments of HIV candidate vaccines
– paragraphs 17-18?
Answer : ____________________________________________________________