ddodell@stjhmc.fidonet.org (David Dodell) (08/21/90)
AIDS TREATMENT NEWS Issue #109, August 17, 1990
Aspirin and AIDS
MAI, Toxoplasmosis Progress Reports
Announcements/News Notes:
New York aspirin trial; California health-fraud legislation
update; Compound Q report; San Francisco study of AIDS
caregivers
Aspirin and AIDS
by John S. James
Since early in the AIDS epidemic, some research has
suggested that ordinary aspirin (or certain aspirin substitutes)
might have a role in treating the disease, other than the relief
of minor symptoms. Aspirin could not be the whole answer, of
course. But laboratory studies have suggested that reducing
certain inflammatory reactions, as aspirin does, may affect the
pathogenesis of the disease, improving some immune functions, and
possibly slowing the replication of HIV by reducing the levels of
certain chemical messengers which may trigger the growth of the
virus. Some anecdotal reports which have come to our attention
also support the possibility that aspirin may have a role in the
treatment of AIDS or HIV.
For several years a number of physicians have used aspirin
or other anti-inflammatory drugs to help patients with AIDS feel
better -- especially to relieve fever or diarrhea when these
symptoms are unexplained, and in some other cases such as fevers
caused by MAI. While aspirin works for these purposes, until
recently the treatment of choice was usually indomethacin, a
nonsteroidal anti-inflammatory drug (NSAID); the reason for
preferring indomethacin is that published information was
available, since most of the early research was done with that
drug. But new research is now suggesting that aspirin might be
better than indomethacin or other NSAIDs. Both provide
symptomatic relief from fever and diarrhea, and both reduce
synthesis of a certain prostaglandin (see explanation below),
which appears to be excessive in persons with AIDS and may make
the disease worse. But aspirin might also have an anti- HIV
effect which indomethacin does not.
Aside from a small study recruiting now, we know of no
clinical trials to find out whether aspirin or similar drugs
might have use in AIDS treatment. Without trials, the
possibility remains theoretical; it is not known what dose, if
any, might be useful.
It may seem impossible that if something as simple as
aspirin might have value in treating AIDS, it could have been
overlooked. But in fact, that outcome would be most likely.
Aspirin is a generic drug, so there is no commercial incentive to
run trials. Governments would have incentive to learn about an
inexpensive treatment, but Federal research is based on letting
scientists decide what they want to study. Usually this is a
good policy, but in AIDS it has led to control of most funds by
small groups of scientists, whose research interests have been
narrowly focused and have been influenced by the availability of
funding from pharmaceutical companies. Few private physicians
conduct their own research without funding, or use treatments not
already accepted as standard of practice and not proven in
clinical trials. The essence of the problem here is that no
person or office has, or ever has had, overall responsibility for
managing government or public-policy response to the epidemic.
Therefore when there are hints that a safe and readily available
treatment may be useful, it is nobody's job to make sure that
those hints are followed up.
Background and Literature Review
Aspirin is considered the prototype of the nonsteroidal
anti-inflammatory drugs. These agents work by reducing the
synthesis of certain prostaglandins (especially prostaglandin
E2), which are part of the inflammatory response. Other drugs
which may be similar to aspirin as potential HIV treatments are
indomethacin (a prescription drug) and ibuprofen (e.g., Advil),
but not acetaminophen (e.g., Tylenol), which is not believed to
have the same effect.
Early in the AIDS epidemic, before the discovery of HIV, a
number of scientists interested in the pathogenesis (origin and
development) of AIDS saw certain inflammatory reactions as part
of the disease process. This approach led to a number of
laboratory studies, which were later published. Most of these
early studies used indomethacin instead of aspirin, probably
because the former was a proprietary drug until 1984 (when it
became generic). After the announcement of HIV, also in 1984,
most research interest focused on it and on nucleoside analogs
like AZT; pathogenesis was neglected. Some indomethacin studies
were published after 1984, mostly in 1985 or 1986 -- probably
reflecting the time required to complete and publish work which
was conceived in the earlier era. (But one study published in
1985(1) was funded by the Gay Men's Health Crisis, which would be
open to funding research on non-proprietary drugs.)
We have only found one abstract on anti-inflammatory drugs
and AIDS or HIV published since 1987. Recent research seems to
be preferring aspirin to indomethacin. A small clinical trial of
a proprietary aspirin derivative, now recruiting at St.
Luke's/Roosevelt Hospital in New York, may provide the first
scientific test in humans of whether or not aspirin can reduce
HIV activity. (See additional information, below, on this
trial.)
A literature search using the Medline computer database
found only nine articles or letters about acetylsalicylic acid
(aspirin) or indomethacin, that were also about AIDS. The
earliest article, in 1984, reported that indomethacin enhanced
the proliferation of lymphocytes from gay men with
lymphadenopathy(2). (Research on immunological effects of
indomethacin, especially in the context of cancer, goes back to
the 1970s.) A 1985 article1 found that the enhanced proliferation
of lymphocytes applied only to cells from persons with AIDS or
ARC, not to those of normal volunteers; the article suggested
that indomethacin might have therapeutic use in treating these
diseases. A 1986 paper(3) found two separate immunological
impairments in cells of patients with KS and AIDS; both were
improved with indomethacin. But a 1987 laboratory study(4) found
no difference between the cells of persons with AIDS or ARC vs.
controls, in the effect of indomethacin; however, this study only
measured production of IL2, a T-cell growth factor, in the
indomethacin test.
Letters from two different groups in Spain concerned
indomethacin for relief of AIDS symptoms. The first, published
in 1986(5), reported experience with six patients with HIV. The
first patient had been treated with indomethacin in 1983, due to
a wrong diagnosis. This patient had generalized lymphadenopathy,
malaise, fever, and severely reduced lymphocyte count; when
treated with 150 mg of indomethacin daily, all symptoms
disappeared, and they had not returned after three years, during
which the treatment was continued. Because of that case, the
physicians tried indomethacin in five persons with AIDS; they
found no toxicity, and four of the five showed "considerable
clinical improvement" after four weeks of indomethacin (the other
patient died of pneumocystis). Two of the four successful
patients needed doses raised to 75 mg every eight hours for the
best results.
The other letter(6) was published in Barcelona in Spanish in
1988. It reported on three patients with AIDS or HIV who were
treated with indomethacin. While all three seemed to be helped
by the drug, two of them had died, one from a recurrence of
pneumocystis, and the other from a recurrence of an unspecified
infection.
Also from Spain, a different research group reported to the
III International Conference on AIDS in Washington, D. C. in
1987(7) that they found increased levels of prostaglandin E2
(PGE2, believed to inhibit immunological functions and possibly
stimulate replication of HIV) in persons with HIV. In HIV
positive patients with depressed cell-mediated immunity, the
level of PGE2 was ten times higher than normal; high levels of
PGE2 correlated significantly with low lymphocyte count, low T-
helper count, and impaired response to mitogens; it was also
observed to correlate with clinical deterioration. (These
observations are significant because both aspirin and
indomethacin are known to reduce PGE2 levels in patients.)
In a computer search of tens of thousands of newspaper and
wire-service stories, we found only one story mentioning a
possible use of aspirin in treating AIDS. An Associated Press
report in 1986(8) quoted researchers from the George Washington
University Medical Center as suggesting that aspirin might be
useful in AIDS and other immunological disorders. Preliminary
trials had found that "one to two aspirin tablets daily can
triple interferon production and double interleukin output."
None of these volunteers were HIV positive, however. (See
"Current Research," below, for more information about this work.)
Two earlier studies, in the 1970s, had found antiviral
effects of aspirin in tests in animals and in plants(9,10).
Current Research
A laboratory study published this May reported a difference
between aspirin and indomethacin in their effect on HIV(11). The
same research group had already reported that intestinal mucosal
cells from persons with AIDS or HIV, taken by rectal biopsy,
would produce p24, a protein of the AIDS virus, during incubation
for 48 hours in the laboratory. The new report found that
indomethacin failed to change the p24 level, while an aspirin
derivative reduced it by half. The researchers speculated that
this effect of aspirin might be related to inhibition of the
enzyme lipoxygenase.
Based on this result, a small clinical trial now recruiting
in New York is testing the aspirin derivative (aminosalicylic
acid, brand name Asacol, an experimental drug now in phase III
trials) as a treatment for non-specific colonic inflammation in
persons with HIV. This aspirin derivative is designed to be
poorly absorbed, and formulated to pass through the stomach
unchanged, so that it can deliver a very large aspirin dose
directly to the intestines. This special form of aspirin is being
used in the research in order to allow a clean study design, but
it is suspected that ordinary aspirin would work, too.
Perhaps the most interesting result of this study will come
later, when the p24 tests are run on the frozen samples. (These
tests are usually run together as one batch, to reduce random
variation caused by laboratory errors.) This data may provide the
first scientific hint on whether aspirin can reduce HIV activity
in patients. Later in this article we suggest other trials which
could be carried out by community-based research organizations,
to answer the question directly, using ordinary aspirin.
For information about a completely different project, we
spoke with Dr. Judith Hsia at George Washington University to
follow up on the 1986 report on aspirin research, mentioned
above. She told us that researchers there are still actively
looking at aspirin as an immune modulator; however, none of the
volunteers so far have been HIV positive. (One of the scientists
in this study, Dr. Allan Goldstein, is also the developer of the
HGP-30 AIDS vaccine.)
A 1989 publication from the George Washington group(12)
documented large increases in levels of gamma interferon and IL2
in normal volunteers after aspirin treatment. The dose was
surprisingly small; 325 mg (one ordinary aspirin tablet) every
other day worked much better than one tablet every day, during
the one week of the study. Later, volunteers were deliberately
infected with a common-cold virus; not surprisingly, the small
aspirin dose did not protect them.
In a current study by the same research team, aspirin is
being given to elderly mice (elderly so that they would be immune
deficient) in order to see if it would make flu vaccine work
better. No results are available yet.
Practical Experience: Interviews with Physicians
Joseph Sonnabend, M. D., is a well-known AIDS physician in
New York and one of the founders of the Community Research
Initiative (CRI), a leading organization in community-based
research. Dr. Sonnabend has long been critical of the
overemphasis on HIV as the cause of AIDS to the virtual exclusion
of other promising research areas such as pathogenesis. He has
used anti-inflammatory drugs for years in treating AIDS and
related conditions.
In our recent interview, Dr. Sonnabend made the following
points:
* He had used indomethacin, because of the experience with
it reflected in published literature (reviewed above). Now he
uses aspirin instead.
* He has used anti-inflammatory drugs when patients are
seriously ill, with recurring fevers not due to opportunistic
infections. (Dr. Sonnabend is notably aggressive about prompt
diagnosis and treatment of opportunistic diseases; anti-
inflammatory drugs must not be used instead of such medical
care.) These patients usually take one gram of aspirin (two 500
mg tablets) four times a day.
Continuous use of this high dose is likely to cause stomach
ulcers, unless another drug is used to protect the stomach. Dr.
Sonnabend uses misoprostol (brand name Cytotec). Another
physician we spoke with preferred sucralfate (brand name
Carafate) to protect the stomach; he was concerned that
misoprostol would reduce stomach acidity so much that the
antifungal Nizoral (used by some AIDS patients) would not work.
Also, Cytotec is expensive. And it is an abortifaciant, so it
cannot be used during pregnancy.
* While there is no scientific proof that aspirin can or
cannot slow the progression of AIDS, it is clear that many
patients feel much better while on the treatment.
* Enteric-coated aspirin -- and also aspirin suppositories
-- are available, and they might be better than the tablets
because they avoid direct irritation of the stomach. (They would
not eliminate the need for a drug to protect the stomach,
however, because high-dose aspirin can cause ulcers through
systemic effects, even without direct contact with the stomach.)
For another view, we called James Campbell, M. D., in San
Francisco. He was aware of the research interest in anti-
inflammatory drugs as immune modulators, but added that they have
been used most extensively to help patients feel better: to
suppress fevers caused by MAI, for example, or to reduce diarrhea
when it is unexplained. With large doses there can be toxicity
to the kidney and to the stomach.
Anecdotal Reports
We have heard four anecdotal reports relevant to aspirin as
a component of AIDS or HIV treatment.
One person with AIDS had fever most of the time, and noticed
that he felt dramatically better when using aspirin. His
physician warned that he should stop, because of the danger of
stomach ulcers. We lost touch with this person over a year ago,
and do not know what treatment he used, or with what result.
Two other people had taken aspirin daily for years, for
reasons unrelated to AIDS, and both had done unexpectedly well in
remaining alive and healthy. One takes two aspirin tablets every
night; we do not know what dose the other uses.
One physician with AIDS told us he tried anti-inflammatory
drugs, without apparent value. He had used both NSAIDs and
aspirin.
Precautions
Continuous use of large doses of aspirin can be dangerous,
and it is important to discuss the risks of this treatment
possibility with one's physician.
Here is a partial list of some of the concerns which have
come to our attention:
* Precautions against stomach ulcers were discussed above.
In addition, aspirin should be taken with "food, milk, antacid,
or large glass of water"(13) to reduce stomach irritation.
Effervescent preparations may be helpful. Alcohol makes the
stomach problems worse, and should be avoided by persons using
long-term aspirin therapy.
* Aspirin delays blood clotting. Persons with hemophilia or
other blood-clotting disorders, or who are taking medications
which affect clotting, must get medical advice before using
aspirin.
* One case of Reye's syndrome in an adult with AIDS who was
using aspirin was recently reported(14). This rare but serious
disease is usually found in children, and aspirin is believed to
increase the risk. The authors had not heard of any other case
in an adult with AIDS.
* Large doses of vitamin C can cause aspirin to be excreted
more slowly, increasing its concentration in the body.
* Aspirin can interact with other drugs.
For these and other reasons, persons should consult their
physician before using large doses of aspirin.
Suggestions for Trials
Community-based research organizations could easily conduct
trials of aspirin in the treatment of AIDS or HIV, and could make
an important contribution by doing so. Here are some of the
trials that we think most need to be done. The goal is to obtain
objective evidence relevant to the usefulness of aspirin in AIDS
treatment.
* Can aspirin reduce HIV replication or activity? One way to
find out would be a randomized trial with p24-positive volunteers
assigned to take aspirin or not to take it. Volunteers could
continue AZT and other medications they were using.
How long would this trial have to run, and how many patients
would be necessary? To find out, an initial pilot study would
watch changes in p24 levels in several patients treated with
aspirin. This pilot data may already be available in existing
medical records.
* Could aspirin have a role in early HIV treatment? Here
most patients would be p24 negative, so p24 could not be used as
a marker of viral activity.
One physician suggested that a good time to try aspirin
might be at around 300 T-helper cells, when the first symptoms of
HIV, such as inflammation in the mouth, were beginning to
develop. He thought that large doses, such as used by persons
with arthritis, would be necessary.
To test this theory, a study could look at T-helper counts,
in patients with starting counts in a range of about 200 to 500.
In this range, the T-cell count appears to be a sensitive
indicator of whether a treatment is working. Different doses
should be tried, to obtain information about dose-response. If a
low dose can be helpful, it would be important to know that.
A pilot study could suggest how much of an effect to expect,
and how long to wait for it. Again, this pilot data may already
be available.
* What is the long-term effect of aspirin on health and
survival? The problem here is to design a study which is feasible
to carry out.
Nobody knows for sure that p24 and T-cell improvements
necessarily predict improved long-range outcome. But to get
statistical proof that a treatment affects "hard" clinical
endpoints like death or disease progression requires a huge study
with hundreds of patients, some randomly assigned to a control
group. For aspirin, no such study will happen.
The alternative of "historical controls" -- comparing
treated patients with others who were not treated in the past --
presents problems because of the changes in the epidemic.
Treatments have changed, and the virus has changed. Patients are
different, too; for example, those now becoming ill were often
infected in the early 1980s, before safe-sex campaigns, so they
are patients in whom the disease has progressed relatively
slowly. But those who became ill in the early 1980s clearly had
a more rapid progression, since the virus had not been prevalent
until shortly before that time; perhaps they were more
susceptible to it. With historical controls, such changes in the
patient population might make a treatment look like it is working
even if it is not.
One approach to this problem might be called a computer-
model control; we believe it was first suggested by San Francisco
AIDS activist Michelle Roland, who occasionally writes for AIDS
TREATMENT NEWS. A computer model would be prepared based on the
best statistical data available about predictors of disease
progression -- the relative importance of T-helper count, other
blood tests, clinical symptoms, use of treatments such as AZT and
OI prophylaxis, information such as age, sex, and race, etc.
Whenever epidemiologists, clinicians, or other experts find
errors in the model, they could correct them, building cumulative
improvements. When they found trends in how the epidemic was
changing over time, they could have the computer mathematically
project the known trends to the present time. Eventually the
model would contain information from thousands of patients,
organized with the ideas of dozens of leading experts.
Then when a clinical trial is designed, the model could
substitute for a placebo control group. All the study volunteers
could be treated; and from their baseline blood work and other
information, the model could predict how many deaths, infections,
or other outcomes would statistically be expected at any given
time in the future, in the absence of any new treatment. (The
methods for making such calculations are well known, as they are
routinely used for actuarial purposes in the insurance industry.)
The group receiving the new drug could then be compared with the
prediction, to see if the drug was working. These trials would
be much easier to organize than those which require a no-
treatment comparison, since patients who would want the treatment
anyway would enroll in the trial to receive consistent followup.
This approach to trial design might be called "smart"
(computerized) historical controls.
Ms. Roland is preparing a proposal for initial development
of such a computer model. Anyone interested can write to her c/o
AIDS TREATMENT NEWS, P. O. Box 411256, San Francisco, CA 94141.
Comment
Until more trials are conducted, it is not possible to be
sure that aspirin can be helpful in treating AIDS or HIV. We are
concerned that as a result of this article, many people will
start taking aspirin. But we are also concerned that a promising
treatment lead is being dropped by default, because of lack of
commercial incentive.
People should be cautious, and tell their physicians about
this or any treatment they plan to use. We also hope that
community-based or other research organizations will organize
trials to obtain definitive information on whether or not aspirin
can help to slow the progression of AIDS or HIV. This treatment
possibility, until now almost unknown in the AIDS community,
deserves serious attention.
Please Send Us Information
If you have any experience with aspirin and AIDS or HIV,
either as a physician or as a patient, please let us know.
Contact John S. James, AIDS TREATMENT NEWS, P. O. Box 411256, San
Francisco, CA 94141, 415/255-0588. We are especially interested
in experience with long-term use, and/or with high doses.
References
1. Reddy MM, Manvar D, Ahuja KK, Moriarty ML, Grieco MH.
Augmentation of mitogen-induced proliferative responses by in
vitro indomethacin in patients with acquired immune deficiency
syndrome and AIDS-related complex. International Journal of
Immunopharmacology. June 1985; volume 7 number 6, pages 917-921.
2. Valone FH, Payan DG, Abrams DI, Dohlman JG, Goetzl EJ.
Indomethacin enhances the proliferation of mitogen-stimulated T
lymphocytes of homosexual males with persistent generalized
lymphadenopathy. Journal of Clinical Immunology. September
1984; volume 4 number 5, pages 383-387.
3. Braun DP, Harris JE. Abnormal monocyte function in patients
with Kaposi's sarcoma. Cancer. April 15, 1986; volume 57 number
8, pages 1501-1506.
4. Hofmann B, Fugger L, Ryder LP, and others. Immunological
studies in acquired immunodeficiency syndrome: effects of TCGF
and indomethacin on the in vitro lymphocyte response. Cancer
Detection and Prevention Supplement. 1987; number 1, pages 619-
626.
5. Ramirez J, Alcami J, Arnaiz-Villena A, and others.
Indomethacin in the relief of AIDS symptoms [letter]. Lancet.
September 6, 1986; 2 (8506), page 570.
6. Salinas Argenta R, Sans-Sabrafen J, Martin E, Zaragoza J.
Indomethacin as symptomatic medication in patients with advanced
HIV infection [letter]. (English translation of title.) Med.
Clin. (Barcelona). April 2, 1988; volume 90 number 13, pages
556-557.
7. Fernando-Cruz E, Fernandez A, Gutierrez C, Garcia Montes M,
Rodriguez M, Zabay JM. Increased levels in plasma of
Prostaglandin E2 (PGE2) could account for the abnormalities of
cellular immune function in drug addicts with HIV infection
[abstract]. III International Conference on AIDS, abstract
number WP. 120.
8. Associated Press. Aspirin may be useful in battling cancer,
AIDS, pregnancy problems. December 3, 1986.
9. Seifter E, Rettura G, Levenson SM, Appleman M, Seifter J.
Aspirin inhibits a murine viral infection. Life Sci. 1975; 16,
page 629.
10. White RF. Acetylsalicylic acid (aspirin) induces resistance
to tobacco mosaic virus in tobacco. Virology. 1979; 99, page
410.
11. Kotler DP, Reka S. Modulation of HIV production by rectal
mucosa in vitro [abstract]. Gastroenterology. May 1990; volume
98 number 5 part 2, page A-457.
12. Hsia J, Simon GL, Higgins N, Goldstein AL, Hayden FG. Immune
modulation by aspirin during experimental rhinovirus colds.
Bulletin of the New York Academy of Medicine. January 1989;
volume 65 number 1, pages 45-56.
13. Nursing89 Drug Handbook. Springhouse Corporation,
Springhouse, Pennsylvania.
14. Jolliet P, Widmann JJ. Reye's syndrome in adult with AIDS
[letter]. Lancet. June 16, 1990; volume 335 number 8703, page
1457.
MAI, Toxoplasmosis Progress Reports
by Denny Smith
Infection with Mycobacterium avium intracellulare (MAI),
also known as M. avium complex (MAC), is a frequent AIDS-defining
diagnosis, and often these infections are disseminated throughout
the body. Several interesting developments have recently been
set in motion for improving the treatment of MAI. They are
surveyed below, followed by highlights of MAI research presented
at the Sixth International Conference on AIDS in June, and an
announcement of a study of a new drug to treat infections of
Toxoplasma gondii. (The last issue of AIDS TREATMENT NEWS, #108,
included a more complete report of treatment news for
toxoplasmosis.)
Azithromycin, an antimicrobial drug which has been discussed
for over two years as a potential treatment for toxoplasmosis, is
now in a pilot study at Pacific Presbyterian Medical Center in
San Francisco to treat MAI. Since this is a pilot study looking
essentially for drug safety, only fifteen persons will be
followed. Participants will receive 500 mg of an oral formulation
daily. When safety is established, trials will begin at other
sites around the U. S.
We spoke to the principal investigator of the study, Lowell
Young, M. D., who is Chief of Infectious Disease at Pacific
Presbyterian Medical Center and Director of the Center's Kuzell
Institute, which will oversee the azithromycin trial. Dr. Lowell
shared several thoughts with us about the future of research for
MAI therapies.
Azithromycin has appeared promising for some time in
laboratory studies for activity against MAI, Toxoplasma, and
Pneumocystis. There may soon be a decision to begin human trials
of the drug for toxoplasmosis. Another new compound, called
clarithromycin, which was disappointing when applied to
Toxoplasma, was shown to be as promising as azithromycin against
MAI in French and German pilot studies. Dr. Young said that the
main distinction so far is that azithromycin remains in the body
longer than clarithromycin. He is eager for trials of both drugs
to progress, but acknowledges the unlikelihood that either of
them alone will be effective against MAI, since the history of
mycobacterial therapies points to a reliance on combinations of
treatments. Both of these drugs are available in some countries
outside the U. S.
The Food and Drug Administration recently granted orphan
drug status to TLC G-65, or Gentamicin Liposome Injection,
manufactured by the Liposome Company. Gentamicin sulfate is
already approved to treat certain bacterial infections, but like
many antibiotics, it does not adequately reach the interior of
human cells, where MAI resides. Liposomes naturally penetrate
cell walls and so are sometimes used to encapsulate and deliver a
given drug to intracellular targets. The use of liposomal
preparations represents a welcome expansion of options to treat
MAI and possibly other opportunistic infections as well. TLC-65
is nearing clinical trials, and interested physicians can call
the manufacturer at 609/452-7060, and speak to Mr. Ed Silverman.
The Houston Clinical Research Network and St. Francis
Hospital in San Francisco are among 16 trial sites nationwide now
recruiting for studies of rifabutin (Ansamycin), an experimental
drug, as a prophylactic measure for controlling latent MAI
infections. (Clofazimine, an approved medication, is another
agent under study for this purpose, given 50 mg daily.) The
rifabutin trials are placebo-controlled. Interested persons in
the Houston area can call 713/528-5554, and in San Francisco
415/775-4321, ext. 2512. Other rifabutin trial sites are located
in Arizona, the District of Columbia, California, Florida,
Georgia, Maryland, Missouri, New Jersey, New York, Ohio,
Pennsylvania, Texas, Virginia, and Wisconsin. Information on
local trials can be obtained by calling the manufacturer, Adria
Laboratories, at 614/764-8382.
The Treatment + Data Committee of ACT UP/New York has
designed a survey for collecting data or opinions from physicians
who have had experience treating MAI. Their successes or failures
with various drugs could provide valuable information when the
results are compiled and studied for trends. To obtain a copy of
the survey, interested persons can call Garance France-Ruta at
212/532-0363, or mail a request to Garance, c/o the PWA Health
Group, 31 W. 26th St., Fourth Floor, New York, NY, 10010. The
analyzed results will be available to participating physicians.
AIDS TREATMENT NEWS has received anecdotal reports from or
about several people who experienced serious hearing loss due to
inner ear nerve damage during treatment with amikacin, one of the
drugs frequently used in MAI treatment regimens. "Ototoxicity,"
including balance difficulties as well as hearing loss, is
already known to be a possible side effect of drugs called
aminoglycosides, which include amikacin as well as gentamicin,
mentioned above. We urge people diagnosed with MAI and their
physicians to be cautious and aware of this potentially
irreversible problem. (Dr. Young told us that the toxicity of
amikacin should be well-known and that it is not usually a worry
when using the drug for less than a month; he noted that the
danger is heightened in older people. The question of whether
the liposomal gentamicin will carry the same risks as the
standard formulation has not yet been answered).
Note: AIDS-related hearing loss is not always caused by
drugs. We have received two other reports of hearing loss, one
caused by lymphoma and the other by candidiasis.
The abstracts published at the recent International
Conference included a study from Chicago which reviewed the
response to treatment in 20 patients diagnosed with disseminated
MAI infections. The treatment used was a common combination of
four oral drugs, administered indefinitely -- clofazimine,
rifampin, ethambutol, and ciprofloxacin -- with an initial
limited course of intravenous amikacin. The authors discerned a
"favorable clinical/microbiological response" to this therapy in
19 of the 20 patients. Bacteremia in four was either controlled
with the addition of amikacin or persisted in its absence. But
three patients experienced severe ototoxicity after 60 days of
amikacin (abstract Th.B. 517).
Another of the abstracts presented at the Conference
discussed the incidence of MAI from a review of the medical
records of eleven pediatric patients at Children's Hospital of
New Jersey. The authors concluded that diagnosis of atypical
mycobacterial infections in children may be delayed for as much
as a year and a half, and that symptoms to watch for are
abdominal distress, persistent fever or failure to thrive
(abstract #2060, Hoyt L and others).
The above items of information may be undramatic by
themselves, but represent a net optimism for controlling MAI.
Only a year ago, many doctors declined to treat this infection at
all, on the assumption that no single drug was convincingly
effective against it. Now AIDS-knowledgeable physicians are
experimenting with various combinations of agents, and we expect
that the ACT UP survey will be of real assistance to them.
566C80 is a new treatment possibility for toxoplasmic
encephalitis, which is entering a pilot study for people who have
already tried the standard therapy, pyrimethamine with
sulfadiazine, but failed to respond or could not tolerate the
side effects. Interested persons should contact Barbara Baird,
R. N., at the National Institute of Allergy and Infectious
Disease, 301/402-0980.
The progress of 566C80, azithromycin, and liposomal drugs
into clinical trials is welcome and long-awaited. If these
agents continue to look useful, we hope the journey from pilot
studies to expanded access is timed to save lives in the very
near future.
Announcements, News Notes
New York: Aspirin-Derivative Trial for Colitis Now Recruiting
A small trial in New York is seeking volunteers to study a
new aspirin derivative, Asacol, for treating intestinal
inflammation in persons with HIV.
Volunteers must be HIV positive, and have colonic
inflammation with no documented intestinal infections -- no
organisms found in stool or tissue samples, in persons who did
not respond to conventional or experimental therapy. They must
meet other medical conditions, such as no history of ulcer
disease or of upper intestinal bleeding, no clotting disorder,
and platelet count at least 50,000. They cannot be taking other
medications for ulcerative colitis or Crohn's disease. Patients
cannot be taking aspirin or aspirin-like medications while on
this trial.
A rectal biopsy will be required for all subjects at the
beginning and at the end of the study. (This procedure, using
flexible sigmoidoscopy after an enema and with mild sedation, is
"safe and uncomplicated," according to the researchers.)
Patients will need biopsy-proven inflammation of the bowel in
order to enroll in the study.
So far, nine patients have been screened, and six have
entered the trial; no toxicities have been found. Two patients
had cryptosporidiosis and did not respond to the treatment; they
are no longer enrolled. Two others felt much better, with
decreased diarrhea and bloating and increased energy. They have
been using the treatment four to five months.
The others started one or two months ago, but it is too
early to see results, which have been seen two to three months
after treatment begins.
For more information about this study, call Anita Tierney at
212/523-3671.
California: Update on Health-Fraud Bill SB 2872
The last issue of AIDS TREATMENT NEWS alerted readers to a
proposed California law that would have allowed property seizure
in cases involving non-approved medical treatments, with proceeds
funding more prosecutions and other government operations. This
bill was not approved at a key legislative meeting on August 7,
and is probably dead for this year. A firestorm of opposition
developed, mostly from cancer activists.
What was most astonishing about the bill's history is that
almost none of its many potential opponents had heard of it until
about two weeks ago -- within days of the last chance to stop it.
The bill had already passed the California Senate unanimously.
Also, there was surprising disagreement among legal analysts
about what the bill would have meant in practice.
Comment
The first lesson from the history of SB 2872 is that
alternative- treatment communities must be better informed about
what is happening in legislatures. Otherwise the most
conservative (and best financed) schools of medical practice will
make the rules in its own interest about what can and cannot
exist.
We also need wider public discussion and debate about what
legislation we want for regulation of unapproved treatments and
medical practice. Most people believe that medical quackery is a
problem. Therefore, a wholly negative approach of opposing all
new legislation is unlikely to be successful. We need more
factual information about case histories of questionable
practices, and what has or has not been prosecuted under existing
laws. Effective participation by all concerned parties will
further the goal of broadly-based public consensus on this issue.
Compound Q: Article on "Underground" Use
The cover story of the August, 1990 issue of the gay/lesbian
newspaper San Francisco Bay Times interviews experts on compound
Q, and focuses on the organizations created by patients to help
people use this treatment. The different sides of this issue
receive a fair hearing -- both the reasons for hope, and the
serious risks, are presented. Much of the information has not
been published before.
To obtain a copy, send a self-addresses stamped envelope to:
Tim Kingston, San Francisco Bay Times, 288 7th St., San
Francisco, CA 94103.
San Francisco: Study of AIDS Caregivers
The UCSF Coping Project, a research study by the University
of California San Francisco, wants to interview gay men whose
partners have AIDS. The goal is to learn from their experience in
order to support caregivers in the future.
For more information, call the UCSF Coping Project, 415/597-
9177.
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