MNSMITH%umaecs.BITNET@uclacn1.oac.ucla.edu (04/07/90)
AIDS TREATMENT NEWS Issue #98, March 2, 1990
CONTENTS
Scabies Increasing, Diagnosis Often Missed
FDA Approves, NIH Recommends AZT for Asymptomatics
Drug Development: What's Needed Now?
Call for Updated Resource List
News Notes: Reticulose, ozone information; AmFAR grants;
Japanese antiviral; Salk vaccine; Koop; Border policy;
Disaster relief bill; San Francisco resource manual;
Project Inform, Community Research Alliance merger
SCABIES INCREASING, DIAGNOSIS OFTEN MISSED
Marcus Conant, M. D., a dermatologist and a leading AIDS
expert in San Francisco, alerted patients at his February monthly
public meeting that he has seen a major increase in scabies in
the last few months, with 20 cases since Christmas. Scabies is
caused by a mite, a small spider which burrows into the skin. It
is very contagious, often transmitted by sexual contact, and
often particularly severe in persons with immune deficiencies.
Scabies is not difficult to treat. The biggest problem is
getting it diagnosed, as physicians often do not look for it.
Historically, scabies becomes widespread periodically; clearly a
major increase is starting now, at least in San Francisco. (We
do not know about other cities.)
Symptoms include severe itching, which may be worse at
night. Itching and rash often start in the web between the
fingers. Other areas likely to be affected include the genitals,
underarms, elbows, and buttocks. Usually the head is not
affected -- but it may be in people with immune suppression.
Treatment requires a prescription cream or lotion (such as
Kwell), often applied everywhere from the neck down and left on
overnight, then washed off in the morning, for four successive
nights. Instructions must be followed carefully; sometimes, for
example, physicians forget to tell patients not to wash their
hands at night, after they have applied the medication. The
mites are often found on the hands, and they can survive there
and re-infect the rest of the body if the hands are not treated.
In addition, clothing and bedding must be collected and
properly cleaned, and all sexual contacts must be treated simul-
taneously, to avoid reinfection.
FDA APPROVES, NIH RECOMMENDS AZT FOR ASYMPTOMATICS
On March 2 the U. S. Food and Drug Administration (FDA) for-
mally approved a change in the labeling of AZT, expanding the
indications for use of the drug to include all adults with HIV
and a T-helper count of 500 or less. For asymptomatic individu-
als, the dose recommended was 500 mg per day (100 mg every four
hours while awake). For those with symptoms, the recommended
dose was higher, the same as for persons with AIDS -- 1200 mg per
day for one month, which may then be reduced to 600 mg per day.
Then, during the next two days, a panel of 19 clinical
researchers, community physicians, and others met at a conference
organized by the U. S. National Institute of Allergy and Infec-
tious Diseases (NIAID) to prepare recommendations for early use
of AZT. This panel made similar, though not identical, sugges-
tions, recommending 500 mg per day for both asymptomatic and
symptomatic individuals. The executive summary from that confer-
ence also includes recommendations on how often to check T-cell
counts for different groups of patients, and on how to manage
persons on AZT.
Both of these government actions have been expected, and the
recommendations are not surprising. A number of physicians,
especially in cities such as San Francisco, have already been
providing early AZT treatment to private patients. The impor-
tance of the FDA and NIAID actions is that it should now be much
easier to get government and private third-party payors to cover
early use of AZT, making early intervention available to many who
otherwise could not obtain it.
About 600,000 people might benefit from early HIV treatment
in the United States alone. Many of them, however, do not even
know that they are infected.
DRUG DEVELOPMENT: WHAT'S NEEDED NOW?
by John S. James
For those familiar with clinical trials and drug develop-
ment, the last few months have been particularly difficult.
Aside from ddI, where the research and distribution programs have
essentially worked and much of the news at this time is good,
research on new treatments appears to have greatly slowed. We
have been unable to confirm that the situation is really as bad
as it appears, however, because of the widespread confusion; no
one seemed to know what was happening. We could not find a
vision or direction for AIDS treatment research, a plan with a
reasonable chance of success.
Now the outlines of how to overcome the current obstacles
and to make research productive again are becoming visible.
Scientifically, what needs to be done is already fairly clear.
In the past, however, the dismal political landscape ruled out
any possibility that what should be done would be done, and led
to the current paralysis. Today elements are in place for new
consensus, new social contracts among the parties involved. This
article describes key elements of consensus which we believe
could and should develop.
What's Wrong Now?
The basic problem has been the expectation that all new
antivirals must go through huge trials, usually scheduled for two
years and requiring hundreds of carefully selected volunteers who
are willing to have their treatment selected at random, before
any drug can be recognized as effective. In practice, enormous
administrative, financial, proprietary, scientific, ethical, and
personnel-shortage problems make these trials take much longer
than two years, and guarantee that the great majority of drugs
worthy of human testing will not be in trials at all.
Early-access arrangements, such as the current test with ddI
or the proposed "parallel track" to provide treatment during the
trials for persons with no other medical options who do not qual-
ify for trials, can save many lives; these vital efforts must be
supported. But early access only works when there is a public-
spirited and well-financed drug company, willing to spend money
to save lives when sales of the drug may be years away. It does
not address the shortage of researchers and facilities caused by
the resource demands of the "dinosaur" (large and slow) trials --
demands which in practice prevent drugs from being tested,
approved, or considered for early access. In short, while we
continue to work for early access, we must also develop more fun-
damental reforms to improve the productivity of the drug testing
and approval system.
What's Needed, And Why It Hasn't Happened Already
The reason for the "dinosaur" trials in the first place is
that disease progression in AIDS is highly variable, and the
laboratory tests to measure progression (such as T-cell count and
p24 antigen) have drawbacks; many researchers have not been wil-
ling to trust these tests to tell whether drugs are working. The
two-year trials with hundreds of patients, comparing deaths and
serious infections in those who do and do not get the new drug,
are used to obtain definitive statistical proof that the drugs
are helping people. The problem, of course, is not only that
these trials take a long time to get results, but also that they
are so unwieldy that in practice they seldom happen at all.
The most important new technology for potentially changing
this situation is the development of better tests of disease pro-
gression, especially plasma viremia (see "New Viral Measurement
for Rapid Drug Testing," AIDS TREATMENT NEWS # 94, January 5,
1990). A small experiment using AZT showed that it was possible
to get definitive statistical proof in a few weeks, with only a
small number of volunteers, that an antiviral is working in
humans to reduce the level of infectious HIV in the blood. If
this kind of test could be used instead of the huge two-year tri-
als required until now, the logjam of AIDS clinical trials could
be broken, and all the important drugs could be tested quickly.
At this time the plasma viremia test is gaining widespread
professional acceptance. The only objections we have heard are
that some researchers question whether the test is quite ready,
and some want to wait for future tests which will be more econom-
ical. And some leading experts believe that plasma viremia isn't
really necessary, because rapid drug testing could have been done
all along, using p24 antigen, despite its drawbacks. The big
problem now with plasma viremia is that it is very expensive,
costing over a thousand dollars per test. Few labs have experi-
ence doing this test, which is not available commercially.
The professional consensus now developing sees plasma
viremia as something useful to do. But should it be used only to
select interesting candidate drugs for the two-year "dinosaur"
trials, or can it be accepted as the proof of efficacy required
for marketing approval? Could a drug be approved with official
labeling stating that it reduces HIV levels in blood, although
clinical benefit has not yet been proved? On this question, con-
sensus has not yet developed either way.
Here is why we believe it is vitally important that the
answer to the latter question be "Yes":
* Avoiding the need for two-year, several-hundred-patient
multicenter efficacy trials could quickly end the current
drugjam, and allow all important antivirals to be tested.
* Additional safety information could be obtained from tri-
als (or supervised access programs) designed to answer safety
questions -- not dredged as a by-product out of trials structured
primarily to get statistical proof of efficacy.
* A major study by the FDA found that all five vitally
important anti-infective drugs recently approved for marketing
were approved based on pivotal clinical trials none of which used
survival as an endpoint. At least some of these trials did use
reduction in microbial levels, instead. AIDS drugs should not be
bottlenecked by unworkable requirements which are not applied to
other drugs.
* Doctors and patients considering using antivirals which
had been proved to reduce HIV (but not proved to increase sur-
vival or reduce opportunistic infections, because those studies
had not been done) would also have other options available,
including AZT, about which much more is known. They can and
should be trusted to decide among these options.
* Further clinical research could be required after market-
ing approval, when necessary.
* Companies with a promising drug would have a realistic
chance to get it to market in the foreseeable future, and make an
attractive but fair profit. (Today, only companies with great
resources and the right connections can seriously hope to do so.)
Incentive would stimulate AIDS drug-development projects
throughout the clinical-trials pipeline, all the way back to the
laboratory, and could get many more companies involved in AIDS
research (only a few are today).
* Competition between drugs would help to control runaway
prices, potentially saving billions of dollars for governments,
other third-party payors, and individuals.
* Faster development of improved treatments could save addi-
tional billions of dollars in hospitalization and other expensive
care -- as well as saving lives.
* The alternative -- continuing to require huge, two-year
trials before drug approval -- is exceptionally grim. U. S. AIDS
drug development is now close to a standstill, and there are no
prospects for finding enough resources to get it going again
under current procedures.
But what if the AIDS researcher establishment will not sup-
port plasma viremia or any other alternative to the years-long,
"dinosaur" trials for meeting the efficacy requirement for mark-
eting approval? If that happens, then the AIDS community should
use the consensus it can get -- that plasma viremia is worth
doing to help prioritize drugs -- and push for parallel track
access to the drugs which this test shows works best. And also,
we would have to examine how much of the objection to a workable
approval system stems from scientific concerns, and how much
stems from the empires which have been built under the present
system. How much results from the influence which Burroughs-
Wellcome (which stands to lose most if alternatives to AZT are
approved for marketing) has purchased throughout the AIDS
research community?
In the past, AIDS researchers were inadvertently given
incentives to build empires, not to get practical results. No
one spoke out when existing procedures, policies, regulatory
standards, and scientific conventional wisdom virtually
guaranteed that no new drugs would be developed. Today there is
much more pressure for results. All the parties involved have a
common interest in improving the productivity and efficiency of
drug development and regulation.
Price Vs. Incentive: Toward A New Social Contract?
Recently we have heard concerns that pressures from the AIDS
community to lower drug prices will deter companies from engaging
in research. We do not know how serious this problem is, but it
is hard to see how price will cease being an issue. Usually those
who want to let companies charge anything, to give them maximum
incentive to develop new drugs, are those who will always get the
treatments they need at any price. But for the great majority,
the price issue will not go away.
Another approach to improving incentives is to make poten-
tial profits more likely, and not as far away in time -- instead
of insuring the right to make exorbitant profits in some hazy,
distant future when the drug in question will probably be
obsolete anyway. Consider the following proposed three-way
understanding between government, industry, and the AIDS commun-
ity:
* In an emergency, the FDA would develop standards designed
to be feasible for pharmaceutical companies to meet, to promote
two public purposes: getting drugs approved sooner, and giving
pharmaceutical companies more incentive to be involved in
research. The FDA is already moving in this direction. It
should explicitly recognize that part of its job is to develop
regulations which stimulate commercial development when required
to meet a national emergency.
* Companies which respond to an emergency must be able to
recover their research costs and make a profit. Some would say
the profit should be above industry average, because of the extra
risks and expenses for an accelerated or even crash program. But
also there must be some restraint. In return for government
assistance, through financing of research, streamlining of regu-
lations, or otherwise, companies with a unique product for a
life-and-death emergency must not be allowed to profiteer and
charge whatever the market will bear. Companies can no longer
take advantage of the bigotry toward AIDS to pioneer unconscion-
able policies, which they then apply to other diseases later.
* The AIDS community should accept reasonable profits (but
not profiteering) for drug companies as a requirement for making
the system work. We cannot wait for a new economy -- either for
socialism or for libertarian free enterprise -- but must make the
existing system work now. We should continue to support com-
panies which are willing to consider the public interest and work
together in mutually beneficial public-private partnerships.
Also, the AIDS community will need to communicate and negotiate
with the consumer-protection movement, and with advocates and
organizations for other diseases, more than it has in the past.
Until last summer, government-funded researchers and FDA
officials had little contact with "front line" private or clinic
physicians with large AIDS practices; now there is much better
communication. This improvement should make the government-
funded research more responsive to practical needs.
Patients and researchers often have different interests;
until recently there was little communication, and often hostil-
ity, between them. Now both groups are learning that they need
to work together.
Today all parties involved in AIDS treatment development
realize that there are serious problems in the current system,
and that consensus and collaboration are necessary to overcome
them. The elements of a new consensus are now taking shape.
CALL FOR UPDATED RESOURCE LIST
Last year AIDS TREATMENT NEWS published a resource list of
PWA Coalitions, Buyer's Clubs and ACT UP chapters. We will be
compiling an updated version soon and want to hear from newly-
formed groups which are part of one of these networks, or serve a
similar function.
NEWS NOTES:
RETICULOSE, OXIDATION THERAPIES:
PROJECT INFORM PUBLISHES INFORMATION SHEETS
In February Project Inform published two separate informa-
tion sheets about proposed AIDS treatments, one on Reticulose,
the other on oxidation therapies (such as ozone and hydrogen
peroxide). Both concluded that the treatments are not useful.
Anyone considering using them should first obtain the Project
Inform writeups, since otherwise it is hard to find any informa-
tion except from the promoters.
To obtain the Project Inform information, call their hotline
at 415/558-9051, from 10 AM to 2 PM Pacific time, Monday through
Friday. Persons within California but outside the San Francisco
local calling area can call toll-free 800/334-7422; from other
States the number is 800/822-7422. Project Inform is a San Fran-
cisco organization which provides information on non-approved
AIDS/HIV treatments.
On June 2 AIDS TREATMENT NEWS described a rectal ozone moni-
toring study organized by patients in San Francisco, with the
assistance of research nurse Leland Traiman. Recently we called
Mr. Traiman, who told us that the study, with 26 patients, was
completed and submitted to the Sixth International Conference on
AIDS. No harmful effects of the ozone treatment were found --
but no benefits were found, either.
About two years ago, AIDS TREATMENT NEWS began research for
an article on hydrogen peroxide. We gave up because of the dif-
ficulty of finding people familiar with the treatment who were
not selling it.
AMFAR GIVES $1.9 MILLION TO AIDS RESEARCH
On February 21 the American Foundation for AIDS Research
(AmFAR) announced awards of almost two million dollars to 24 AIDS
research projects. Most are laboratory studies in virology or
biochemistry.
On January 27 AmFAR announced separate awards totalling $1.1
million to 12 community-based clinical trials centers. These
emergency grants were to help the organizations survive an unex-
pected shortage of Federal funds.
AmFAR has given a total of $24 million to over 350 research
teams and educational projects since its founding in 1985.
JAPANESE COMPANY DEVELOPS NEW AIDS ANTIVIRAL
Mitsubishi Kasei Corporation, together with the Katholieke
Universiteit Leuven (Belgium), the University of Birmingham (Eng-
land), and Showa University in Tokyo, has developed an AIDS
antiviral which, according to a February 16 Reuters report, the
company hopes to enter into U. S. clinical trials before the end
of 1990.
A technical report on the potential drug, called HEPT
(hydroxyethoxy methyl phenylthiothymine) appeared in Biochemical
and Biophysics Research Communications, December 29, 1989, pages
1375-1381. The antiviral worked in both T-cells and macrophages
infected with HIV-1, but did not affect HIV-2 or other viruses.
How it works is not known.
SALK VACCINE COMPANY SELLS FOREIGN RIGHTS
In an agreement announced on February 28, two major medical
research institutions in France, the Institut Merieux and its
subsidiary Pasteur Vaccins, have jointly purchased rights to
market the Salk HIV vaccine outside of North America. (The U. S.
company developing the treatment, The Immune Response Corporation
of San Diego, CA, has arranged separate North American marketing
with Rorer Group, Inc.)
Unlike most vaccines, the Salk HIV vaccine is intended to be
used after persons are already infected. This treatment, called
AIDS Immunotherapeutic, is currently in clinical trials in the
United States.
Despite the reputation of Dr. Jonas Salk, who developed the
first polio vaccine, his HIV work has been slow to receive sup-
port in the U. S. AIDS research establishment.
Institut Merieux is the leading marketer of vaccines in the
world.
KOOP CALLS U. S. AIDS POLICY "ALMOST TEN YEARS OVERDUE"
On February 27 C. Everett Koop, former U. S. Surgeon Gen-
eral, told Congress that "We don't have a Federal policy on AIDS,
period," and that unless Congress intervenes, the situation will
only get worse. Dr. Koop was speaking to the House Subcommittee
on Health and the Environment, in support of a bill to expand
Medicaid coverage for persons with AIDS or HIV.
Dr. Koop called it "incredible that the Federal government
has not had a dialog with the states, and with certain municipal-
ities," about how the costs of the epidemic will be paid.
Representative Waxman (D-California) commented that "Having
missed the opportunity to get the ounce of prevention, we now
have to pay for pounds and pounds of cure."
CENTERS FOR DISEASE CONTROL URGES END TO HIV BORDER EXCLUSION
On March 1 the U. S. Centers for Disease Control recommended
that all diseases except one be removed from the list of condi-
tions used to exclude persons from entering the United States.
Only tuberculosis would remain grounds for exclusion.
However, HIV differs from all the other diseases in that it
is the only one added to the list by Congress. (The others were
added by public-health professionals.) U. S. officials believe
that since Congress specifically put HIV on the list, only
Congress can remove it. It may not be possible to do so in time
to avoid disrupting the major AIDS scientific conference of 1990,
scheduled for June 20-24 in San Francisco.
SENATORS PROPOSE AIDS DISASTER RELIEF FOR CITIES AND STATES
On March 6 Senators Edward Kennedy (D-Massachusetts) and
Orrin Hatch (R-Utah) introduced a bill to provide $500 million
disaster relief to areas heavily impacted by AIDS. The bill is
patterned after relief programs for areas hit by disasters like
earthquakes and hurricanes -- for example, the $3 billion
appropriated by Congress for the recent earthquake near San Fran-
cisco. Both California senators, Alan Cranston and Pete Wilson,
are among 18 co-sponsors of the bill.
About half of the money will go to 13 cities which together
have about 60 percent of the U. S. cases of AIDS: Atlanta, Bos-
ton, Chicago, Dallas, Houston, Los Angeles, Miami, Newark, New
York, Philadelphia, San Francisco, San Juan, and Washington, D.
C. The rest of the money would go to states, depending on their
numbers of AIDS cases. Different areas will be able to use the
money to develop the kinds of programs most suitable for them.
If the bill becomes law in its current form, San Francisco
will receive about $40 million for AIDS disaster relief.
SAN FRANCISCO AIDS SERVICES: NEW RESOURCE MANUAL
The San Francisco AIDS Foundation has published an 85-page
updated edition of AIDS and ARC: A Resource Manual. It lists
services available in San Francisco in January 1990.
Dozens of financial, medical, mental health, and social ser-
vices are included. Over 25 chapters cover topics such as enti-
tlement programs, emergency funds, hospitals, clinics, alterna-
tive therapy information, referral, crisis intervention, spiritu-
ality, childcare, housing, home care, insurance benefits counsel-
ing, political and social organizations, transportation, and
legal services. Information includes addresses, phone numbers,
description of services, and eligibility requirements. Organiza-
tions are also listed alphabetically in the index.
For copies, call the San Francisco AIDS Foundation, 415/861-
3397. Note that this manual lists only San Francisco services.
PROJECT INFORM AND COMMUNITY RESEARCH ALLIANCE WILL MERGE
Two San Francisco community-based AIDS research organiza-
tions, Project Inform and Community Research Alliance, have voted
to merge in order to carry out research more effectively. Pro-
ject Inform, active since 1985, provides AIDS treatment informa-
tion through a hotline (see phone numbers in the other Project
Inform article in this News Notes section) and publishes a
newsletter (PI Perspectives); last year it organized a study of
the Compound Q being imported by patients from China. Community
Research Alliance, founded in 1988 as a project of San
Francisco's PWA Coalition, organized an institutional review
board and scientific advisory committee, and took other steps
legally or otherwise necessary to carry out clinical trials. It
conducted the hypericin monitoring study reported in AIDS TREAT-
MENT NEWS issue #96, February 2, 1990.
This merger was consistent with the widespread belief that
AIDS organizations should consolidate to provide services more
efficiently. In this case, the savings is not in staff or facil-
ities, but in avoiding the need to duplicate the building of a
public identity and funding base for separate organizations with
the same purpose.