MNSMITH%umaecs.BITNET@uclacn1.oac.ucla.edu (04/07/90)
AIDS TREATMENT NEWS Issue # 97, February 16, 1990
CONTENTS:
TIBO Derivatives: Most Selective Antiviral?
New Threats to AIDS Research Funding
Neuropsychiatric Effects in AIDS
"Expanding Access to Investigational Therapies" Conference,
March 12-13 in Washington, DC
AIDS Service Organizations: New National Directory
News Notes: Life Expectancy; Epidemiology; Fluconazole; Kenya
TIBO DERIVATIVES: MOST SELECTIVE ANTIVIRAL?
Researchers in Belgium and the U. S. have developed a new
antiviral which appears to act more selectively against HIV than
any other known chemical. Early results were published February
1 in Nature, which is widely considered to be the world's most
prestigious scientific journal.
In an important departure from research procedures enforced
in the United States, this early report includes not only labora-
tory results but animal and human safety information as well.
After developing a drug (so far known only as R82150), research-
ers gave dogs a thousand times the dose likely to be effective,
with no adverse effects. Then six healthy volunteers took a sin-
gle 200 mg dose orally; blood levels sufficient to inhibit HIV
were maintained for over 24 hours, with no toxicity. No test with
persons with AIDS or HIV was reported. But this initial human
experience could greatly speed future development of the drug,
because a huge psychological and legal barrier -- the reluctance
to try a new chemical in humans for the first time -- has already
been crossed.
In the laboratory, R82150 inhibited HIV in concentrations
about 31,000 times less than those toxic to cells; a comparable
value for AZT was about 6,200. The drug was effective against
five different strains of HIV-1, but was so selective that it did
not act against HIV-2, or against any other virus tested. R82150
is believed to inhibit reverse transcriptase, like AZT; but
unlike AZT, it is not a nucleoside analog. R82150 is difficult
to manufacture in quantity by currently known techniques.
R82150 was developed in Belgium, at the Katholicke Universi-
teit in Leuven, and the Janssen Research Foundation in Beerse.
The drug-development strategy was to start with 600 basic
molecules, and then use intelligent trial and error to synthesize
related chemicals to find ones which are more effective in
laboratory assays. 'TIBO' is an abbreviation for the name of one
of the chemicals.
Until the drug is tested on persons with AIDS or HIV, it is
not possible to know whether it will be effective. We do not
know what clinical trials are planned.
NEW THREATS TO AIDS RESEARCH FUNDING
by John S. James
A growing chorus of voices in Washington and in the media is
saying that AIDS has unfairly been given special treatment, that
the epidemic is not as serious as had been believed, and that
money should be taken away from AIDS research and distributed to
other diseases or other purposes.
AIDS TREATMENT NEWS focuses mainly on scientific and medical
information about treatment, and on how to design and administer
research to get results, rather than on funding issues. But many
arguments now being circulated to support reduced AIDS funding
are one-sided or worse, and so far the other views are not being
widely heard. This article outlines some of the issues in the
current funding debate, in order to provide a more balanced view
and help our readers support attempts to deal with AIDS through
effective research, prevention, and treatment, instead of by
writing off certain populations and dismissing the epidemic as
not a concern to the majority.
The Case Against Research Funding
Much of the case for reducing AIDS treatment research was
summarized in an article published last month in Time magazine
("The AIDS Political Machine," January 22). It made the follow-
ing arguments:
* The Federal AIDS budget of $1.6 billion is greater than
that for cancer ($1.5 billion), although cancer killed 12 times
as many people last year. The article also quoted without chal-
lenge a statement by Michael Fumento, author of The Myth of
Heterosexual AIDS, that AIDS would never kill more than 35,000 to
40,000 people a year.
* Twice as much money is being spent on drug development as
on prevention of transmission, although experts believe that
prevention, not treatment, should be the key to stopping the epi-
demic.
* Money targeted to AIDS reduces funding for other diseases.
* Traditional principles of drug approval are being "dis-
torted." The article's prime example: that AZT was approved in
less than four months, compared to an average of two years. The
article invoked the memory of Laetrile, a discredited cancer
treatment, to suggest that changes to speed FDA drug approval
threaten to leave the public vulnerable to quack cures.
* "AIDS has a far greater impact than the number of its vic-
tims (sic) would dictate" -- implying it has been overemphasized
-- because of the money, organization, and articulateness of the
gay community.
Another common argument against AIDS funding, which did not
appear in the Time article, is that the public need not pay for
AIDS because it was acquired by people's voluntary behavior and
therefore is their fault. This argument ignores the fact that
the average time from infection to AIDS is about nine years, and
highly variable, while the disease was unknown until 1981, the
virus not announced until 1984, and prevention information was
not widely disseminated until later. Most of those now ill were
infected before they had any warning of how to protect them-
selves. Much of the public does not know that persons now ill
were infected years ago, but those quoted as AIDS opinion leaders
almost certainly do. Apparently this argument against paying for
AIDS has been spread even when it was known to be false.
The Other Side
Here is some of the information omitted from the Time arti-
cle and from similar attacks on AIDS funding:
* The comparison of the money spent for AIDS and cancer is
misleading. According to a fact sheet prepared by the Human
Rights Campaign Fund in Washington, D. C., the $1.5 billion for
cancer only includes the spending of the National Cancer Insti-
tute, part of the National Institutes of Health (excluding spend-
ing for AIDS-related cancer research). But the $1.6 billion AIDS
figure includes not only the entire National Institutes of Health
(including the NIAID clinical trials, AIDS spending in the
National Cancer Institute, and much basic biomedical research
sometimes arbitrarily counted under AIDS), but also the Centers
for Disease Control, the Food and Drug Administration, the Health
Resources and Services Administration, and the Alcohol, Drug
Abuse, and Mental Health Administration. If cancer spending in
the National Cancer Institute alone is compared with AIDS spend-
ing in the entire National Institutes of Health -- a comparison
which still exaggerates the relative money spent on AIDS -- then
cancer receives twice as much money as AIDS, $1.5 billion vs.
$750 million.
* The cancer infrastructure has been built over decades,
whereas the AIDS infrastructure had to be created from scratch
during the last few years in which funding was available. It is
unfair to ignore this difference when comparing recent funding
only. And cancer is really many different diseases; comparing
cancer with AIDS can obscure more than it reveals.
* Spending on AIDS is comparable to that for other diseases
in research dollars spent per year of life lost.
* The four months to approve AZT vs. two years average for
drugs refers to the time taken for government paperwork, not
scientific research. Although figures are not available, it is
likely that most of the cited two years is due to inadequate
staff at the FDA, causing drugs to wait in line while nothing
happens. Until staff shortages can be corrected, it is essential
to give vitally important new drugs for any disease priority over
marginal or "me too" product introductions. This kind of reform
does not weaken the approval process or threaten to introduce
quack remedies.
* AIDS is spreading rapidly in many communities and will
certainly kill more people in the future than it is killing
today. Research funding should consider not only today's deaths,
but the future as well.
* Aside from all these specifics, the thrust of some current
efforts to compare dollars for cancer vs. AIDS is to get the dif-
ferent disease lobbies fighting among themselves, when everyone
would benefit if we could work together better as a coalition.
We should remember that the entire budget of the National Insti-
tutes of Health, for all diseases combined, is $7.6 billion, less
than the current year's cost of only two military systems, the
Strategic Defense Initiative ("Star Wars," at $3.8 billion), and
the B-2 bomber ("Stealth," at $4.3 billion). Which effort is
more cost-effective in saving the lives and protecting the qual-
ity of life of U. S. citizens? Which is the better use of the
same tax dollars -- Star Wars and the Stealth bomber, or all
Federal biomedical research on all diseases conducted by the
National Institutes of Health? This country can afford adequate
medical research; the real issue is national priorities, not
whether money is available.
* The Time article suggested that money should be spent on
prevention rather than drug development. It quoted an ACT UP
member to portray the AIDS movement as focusing on treatment
instead of prevention, implying that people with AIDS or HIV by
trying to save their own lives are distorting the national
response to the epidemic, thereby threatening the lives of
"blacks and Hispanics of the inner cities of the East." But in
fact the gay community has long been in the forefront on preven-
tion, and the AIDS movement has emphasized prevention far more
than treatment, which only recently became a priority. The scan-
dalous delays in prevention have not resulted from money being
spent on drug development, and are not at all the fault of the
(mostly gay) AIDS movement, which the Time article has framed as
a threat to the lives of members of other groups. Anyone
involved in prevention knows that the bottleneck has resulted
from consistent, long- standing political obstructionism by cer-
tain conservatives and fundamentalists. But those unfamiliar
with the history of what is actually happening could take from
the Time article images divorced from the facts.
* Another argument for reducing AIDS funding is that the
epidemic is not affecting as many people as had been predicted.
For example, new AIDS cases reported in 1989 to the Centers for
Disease Control were only nine percent above the total reported
for 1988 -- a much lower rate of increase than in previous years.
And according to another recent report, an unexpected change for
the better seems to have started in mid 1987.
But much is still unclear. For example, nobody knows for
sure why the improvements have occurred; there are at least five
different theories, each with its own proponents (safer sex,
availability of treatments, underreporting, changes in the defin-
ition of AIDS, or estimates not being comparable because the ori-
ginal ones were erroneous). This good news does not justify
seizing on new and uncertain information, sometimes before it is
even proofed and published, in an unseemly rush to take money
away from AIDS.
* Another argument (not in the Time article) for de-
emphasizing AIDS is that the disease is not spreading rapidly in
the heterosexual community -- meaning white, middle class
heterosexuals in the United States. Aside from the ethical
objections to writing off other populations, there are epidemio-
logical reasons to be careful of telling the white middle class
that it has little to worry about. In Africa AIDS is spread
almost entirely by heterosexual contact, including in the middle
class. In parts of Latin America, AIDS is in transition from the
U. S. /European pattern (gay men and IV drug users) to the Afri-
can pattern (heterosexual transmission), showing that this change
can happen. And in the U. S., syphilis has reached its highest
rate in 40 years, mostly among heterosexuals -- showing that peo-
ple are not being careful, and also providing genital sores which
are believed to facilitate epidemic heterosexual transmission. A
major heterosexual epidemic in the United States cannot be ruled
out, and after it starts, it may be too late to stop. Now is not
the time to encourage people to let down their guard by telling
them that AIDS is someone else's problem.
Toward Coalition and Consensus -- And a Demographic Obstacle
The current push to de-emphasize AIDS research is objection-
able not only for its factual distortions, but for what it is
trying to do. It is seizing every excuse to try to write off and
abandon people with AIDS or HIV, divide the spoils among other
interests, and dismiss what AIDS has taught us about weakness in
the health-care and research/approval system, and about how to
begin to change them. Instead of encouraging disease groups to
fight each other, we should be working together to improve health
care for all.
One demographic obstacle to building such coalitions has
not, we believe, been pointed out before. It appears that almost
everyone working in AIDS is under 40. A major underlying prob-
lems in mobilizing public support and understanding for AIDS may
stem from the tendency of older people not to listen to younger
people or take their concerns seriously. And AIDS organizations
had to be created from scratch, without benefit of the leadership
of those who were older and more experienced, as the older people
were not there. The result may have been the development of
organizations which are not comfortable for the senior people who
are usually the leaders in U. S. institutional life. These
leaders are used to being in charge. They are not inclined to
learn the ropes from younger activists, as may be necessary in
AIDS since usually older people are not involved.
This same dynamic may also explain failures of mobilization
within the medical community. Most physicians involved in AIDS
are too young to have major influence in the medical profession
as a whole. They could not speak out effectively to correct such
problems as unworkable clinical-trial designs, irrational bar-
riers to access to necessary treatments, and national research
programs which could not possibly save their patients' lives.
The senior physicians who could have provided this leadership
were not involved in AIDS.
One pioneering effort to bring in leaders from other fields
is the Mayor's HIV Task Force in San Francisco. It spent a year
investigating AIDS here, and then produced a short report with no
surprises. The real significance of the project is that it
involved leaders from the business and religious community who
had not been familiar with AIDS before, and then developed con-
sensus on needs and recommendations.
Those of us who work constantly with AIDS may not realize
how extensive a subculture has developed. This writer, for exam-
ple, had thought that a few meetings and a little reading would
be enough to bring leaders from other fields up to speed in AIDS.
Instead it took more than a year, in a specially- designed pro-
ject sanctioned by San Francisco's mayor.
We hope that the identification of this problem of the
absent older generation in AIDS will contribute to the creative
thought and experimentation which will be needed for its solu-
tion.
NEUROPSYCHIATRIC EFFECTS IN AIDS
by Denny Smith
A wide range of mental status changes has been attributed
directly or indirectly to HIV. Several recent studies have shown
that asymptomatic people with HIV do not have deficits in cogni-
tive or physical skills when compared to control groups without
HIV. Some instances of disorientation, short-term memory loss,
diminished motor coordination and withdrawal or personality
changes can be symptoms related to HIV disease, and all are
potentially treatable given an accurate diagnosis.
Joyce Seiko Kobayashi, M. D., addressed the neuropsychiatric
aspects of AIDS at the Fifth Annual Rocky Mountain Regional
Conference on AIDS, February 2-3 in Denver. Using a tree-like
graph to rule out unlikely causes for a given symptom in order to
isolate the source of the problem, Dr. Kobayashi distinguished
several symptom categories to consider -- depressed emotional
frames of mind, delirium episodes from acute illness or drug
reactions, AIDS-related dementia, and opportunistic tumors or
infections in the central nervous system.
Depression in people with or without HIV can be an appropri-
ate reaction to anxiety surrounding a health crisis, or grief for
the loss of lovers and friends, or fears of powerlessness over
the future. Dr. Kobayashi facilitates discussion groups for HIV
positive people to deal with these emotions and seek solutions
with the validation of peers.
Mental status changes resulting not from social but from
organic reasons may be imminently life-threatening, and should be
diagnosed and treated as soon as possible. These include crypto-
coccal meningitis (see AIDS TREATMENT NEWS #49 and 96); encephal-
itis or swelling of the brain due to toxoplasmosis (issue #79),
herpes or CMV (issues #94 and 95); or lesions in the central ner-
vous system including PML (issue #88), KS (issues #73, 75, and
87) or lymphoma (issue #93).
Cognitive problems which are not a result of opportunistic
tumors or infections, but from direct HIV invasion of the central
nervous system, are defined as "dementia," or AIDS Dementia Com-
plex (ADC). One theory suggests that HIV damages microglial
cells in the brain. Unlike neurons, which are the irreplaceable
reservoirs of memory and consciousness, microglial cells function
primarily as connections between neurons and can regenerate if
the source of their destruction is controlled. A different
theory says that HIV-infected cells produce toxins which cause
the dementia. AZT, proven to cross the barrier between the
bloodstream and the central nervous system, can reverse the
dementia caused by HIV, although the new, reduced doses might not
be sufficient. Dextroamphetamine and Ritalin are also used to
treat mental effects of HIV.
In addition to depression, organic diseases and dementia,
some transient mental states are considered a "delirium." Side-
effects of some toxic drug reactions, as well as prolonged, high
fevers, can alter lucidity and lead to a delirium. Because many
of these symptoms and their origins may mimic or overlap each
other, Dr. Kobayashi noted that reliance on an AIDS- knowledge-
able physician is crucial for determining a diagnosis and
therapy.
A doctor who is unfamiliar with a newly symptomatic patient
or current HIV care may not accurately distinguish whether memory
gaps and lethargy are stemming from demoralization or a rapidly
progressing brain infection, whether an apparent motor control
deficit is due to cerebral KS lesions or a recent change in medi-
cations, or whether Xanax or a new living situation are in order
for a long-depressed person. Mutual trust developed between an
HIV-experienced physician and an HIV- positive patient can offer
each a background familiarity from which to weigh confusing
situations.
For an audiotape of Dr. Kobayashi's presentation, call
"Sounds True," 303/449-6229. The tape number for her presenta-
tion is AP-27.
"EXPANDING ACCESS TO INVESTIGATIONAL THERAPIES" CONFERENCE, MARCH
12-13 IN WASHINGTON, D. C.
The Institute of Medicine of the National Academy of Sci-
ences will hold a conference March 12-13 in Washington, D. C., on
issues of early access to experimental treatments.
Panel topics include the "treatment IND," whether the philo-
sophy of drug regulation is changing from beneficence to patient
autonomy, cost and insurance coverage issues, how to allow access
and also gather data, reaching the disenfranchised through clini-
cal trials, and the parallel track and what it should accomplish.
For more information, call Gail Spears at the National
Academy of Sciences, 202/334-2453.
AIDS SERVICE ORGANIZATIONS: NEW NATIONAL DIRECTORY
An excellent directory of AIDS service organizations in U.
S. states and cities, as well as several categories of national
organizations, has been published by The United States Conference
of Mayors.
The California listing, for example, includes 39 AIDS organ-
izations in Los Angeles and 86 in San Francisco. It also
includes listings for 78 other cities and towns in the state.
Each listing includes address, phone, contact person, and ser-
vices.
Other lists include national organizations, state AIDS coor-
dinators, state and local service directories, local PWA
chapters, selected service organizations, AIDS minority projects,
community-based clinical trials organizations, NIAID AIDS
research centers, and sources of treatment information.
The directory was prepared by the United States Conference
of Mayors AIDS Program, the Fund for Human Dignity, Inc. and the
National Association of People with AIDS. Support was also pro-
vided by the U. S. Centers for Disease Control, and the Design
Industries Foundation for AIDS (DIFFA).
Copies of Local AIDS Services: The National Directory can
be obtained from the U. S. Conference of Mayors, 1620 Eye Street,
NW, 4th Floor, Washington, DC 20008, 202/293-7330, Attn: Phyllis
Dickerson. The cost is $15 prepaid.
NEWS NOTES
* San Francisco study shows longer life expectancy for peo-
ple with AIDS. A study by epidemiologist Dr. George Lemp and
others at the San Francisco Department of Public Health, pub-
lished January 19, 1990 in the Journal of the American Medical
Association, showed that by 1987, median survival for all
patients diagnosed with AIDS had increased from 12.5 to 15.6
months from time of diagnosis; patients with pneumocystis had a
median survival of 17.9 months. (Later data is not available,
because of the time required for survival trends to become
known.) Median survival of patients treated with AZT was 21.3
months, compared to 13.9 months for those not on any anti-viral
therapy.
San Francisco is generally agreed to have the most accurate
data anywhere on the HIV epidemic.
* The rate of increase of AIDS in the United States slowed
last year. The U. S. Centers for Disease Control reported that
new cases of AIDS in the U. S. increased only nine percent in
1989, compared to a 34 percent increase in 1988 and 60 percent
increase in 1987. Experts attributed the slowing increase to
reduction in new cases among gay men (probably due to prevention
education of years ago), and also to the use of treatments, such
as AZT and aerosol pentamidine, which are preventing some
infected persons from progressing to AIDS. Cases due to
heterosexual transmission rose much more rapidly, however, show-
ing a 27 percent increase last year. The region with the most
new AIDS cases was the South, with 31 percent of the cases.
* Fluconazole will be donated to AIDS and cancer centers.
Pfizer Pharmaceuticals, the developer of the antifungal flucona-
zole, announced that it would donate 6,000 bottles of the drug to
over 200 cancer and AIDS treatment centers in the United States.
According to the February 6 announcement, the drug should be
available now.
* Researchers in Kenya claim success with new drug. The
director of the Kenya Medical Research Institute, Dr. Davy Koech,
told a Nairobi press conference that a drug called Kemron, a form
of alpha interferon, had been given to 101 patients with AIDS or
HIV infection. Only one (apparently out of the first 40 for whom
the longest followup is available) failed to show improvement.
The drug is supposed to reduce or eliminate symptoms of AIDS,
usually within four weeks, but not cure the disease. No indepen-
dent confirmation of its effectiveness is yet available.
Amarillo Cell Culture Co. in Amarillo, Texas collaborated in
this study, which used a natural interferon manufactured by
Hayashibara Biochemical Laboratories in Japan, where it is
approved for treating certain cancers. The drug was given orally
but not swallowed. Very low doses were used, 50 to 150 IU; as a
result, the treatment is inexpensive. This therapy was suggested
by veterinary experience in the U. S. and in Africa.
The Kemron story was carried by Reuters news service, Febru-
ary 7, and was reported in Japan and other countries, but
apparently not in the United States.
STATEMENT OF PURPOSE
AIDS TREATMENT NEWS reports on experimental and complemen-
tary treatments, especially those available now. It collects
information from medical journals, and from interviews with
scientists, physicians, and other health practitioners, and per-
sons with AIDS or ARC.
Long-term survivors have usually tried many different treat-
ments, and found combinations which work for them. AIDS Treat-
ment News does not recommend particular therapies, but seeks to
increase the options available.
We also examine the ethical and public-policy issues around
AIDS treatment research and treatment access.
Copyright 1990 by John S. James. Permission granted for non-
commercial reproduction.