info-aids@apple.com (INFO-AIDS MAILER) (09/17/89)
AIDS TREATMENT NEWS Issue # 87, September 8, 1989
CONTENTS: [items are separated by "*****" for this display]
Antiviral Found in Blue-Green Algae
Interferon, HIV, and Kaposi's Sarcoma Update
The National AIDS Update -- Conference October 10-14 in San
Francisco
New York: PWA Health Group Public Forum, September 27
San Francisco: "Mother, Mother" Benefit for Community
Research Alliance, Family Link, September 28
AIDS TREATMENT NEWS Coming in Book Form
*****
Antiviral Found in Blue-Green Algae
by John S. James
Scientists at the U. S. National Cancer Institute and the
University of Hawaii have discovered a class of anti-HIV chemi-
cals in certain species of blue-green algae, some of them found
in the ocean off Hawaii or off the Palau Islands. This discovery
was reported last month in the Journal of the National Cancer
Institute (Gustafson and others, "AIDS-Antiviral Sulfolipids from
Cyanobacteria (Blue-Green Algae)," pages 1254-1258, August 16,
1989). No one yet knows whether these substances can become use-
ful drugs, but they have been selected for high priority for
further research by the National Cancer Institute.
Background
The chemicals, called sulfolipids (or sulfonic acid-
containing glycolipids) were previously known, but not known to
be antiviral. The recent discovery resulted from a National
Cancer Institute program to search systematically for new AIDS
and cancer drugs which might be found in algae.
Plants have been used as sources of medicines throughout
history, but algae have been largely unexamined, because they are
difficult to work with. Now that it is possible to collect and
test large numbers of species, researchers may find important
medicines which could not have been discovered earlier.
In the current program, the algae species are collected from
a research ship, or on land, and grown in the laboratory to
assure a future supply. If crude plant extracts show potential
value in laboratory assays, then chemical "fractionation" pro-
cedures are used to divide the extracts into different groups of
compounds. Antiviral assays are used to determine which of the
different components includes the antiviral, and this process can
be repeated to find the pure chemical(s) which have the desired
effect.
After the sulfolipids were identified, researchers spent a
year trying to synthesize them, but without success, according to
a report in The New York Times, August 16. Currently, lack of
supply is the major problem delaying drug development, since the
laboratory used so far is set up for screening, not mass produc-
tion. After supplies are obtained, animal studies and other
pre-clinical work will be done before human trials.
Navy Expels Ship
In April of this year, the U. S. Navy interrupted this
research program by expelling a Soviet research ship which would
have carried U. S. and Soviet scientists searching for algae near
Hawaii. Although the project included the National Cancer Insti-
tute and had been approved by the State Department, the Navy
feared that the ship would spy on U. S. military installations.
The captain was given one hour to leave Hilo, where the ship was
docked, and was forbidden to enter Hawaiian waters. Some of the
U. S. scientists rushed off the ship; others stayed on, but were
unable to carry out the 10-day research trip at the planned loca-
tions.
This incident was reported by Honolulu newspapers, and also
by science writer David Pearlman in the San Francisco Chronicle
on May 6, but otherwise it had little or no coverage in the U. S.
press. (The sulfolipids had already been discovered in algae
picked up in an earlier voyage.)
Dr. Gregory Patterson, one of the researchers who found the
sulfolipids, told AIDS TREATMENT NEWS that it is impossible to
estimate the importance of the cancellation of the planned trip,
since the project is looking for completely new drugs from algae.
It is impossible to know the value of what might have been found.
Could Eating Plant Sources Be Beneficial?
Seven different species of blue-green algae -- named in the
article cited above -- were found to inhibit HIV; all contained
sulfolipids. In two species, the sulfolipids were about ten per-
cent of the "organic extractables" from the algae. The different
sulfolipids tested were all about equally active as antivirals,
protecting cells from infection in concentrations of about 1 to
100 micrograms per ml, depending on what kinds of cells were used
to grow HIV. Sulfolipids have been known since 1959; the recent
article cited earlier published research which found that they
occur widely in higher plants, as well as in algae.
AIDS TREATMENT NEWS contacted two of the researchers (one
indirectly, through the National Cancer Institute press office)
to find out if there was any information about whether the chemi-
cals, related to fatty acids, could be absorbed if taken orally.
Both scientists insisted that it is much too early to consider
using these chemicals as drugs, before any animal studies have
been done. Dr. Patterson pointed out that there is much varia-
tion between different species of plants, that the chemicals may
be broken down in the body, and that as there have been no toxi-
city tests, there may be unknown toxicities.
Of course it will be a long time before sulfolipids get
through the drug-development process and (if found effective)
onto pharmacy shelves. Meanwhile there will certainly be an
interest in whether a treatment could be developed using herbal
sources.
One way to minimize the risk of any such attempt would be to
look for plants which have already been used as human food or
medicine, and which also contain high levels of sulfolipids. The
plants would not necessarily be algae. The first step in this
research would be to search the scientific literature to find
what plants are already known to contain sulfolipids; the refer-
ences in the article cited above would be a place to start. It
may also be necessary to chemically analyze likely candidates
(the tests required have been published), to determine which
plants are the best sources.
At least two species of blue-green algae -- spirulina, and a
species from Klamath Lake, Oregon -- are sold as health foods in
the United States. We do not know whether or not either contains
sulfolipids.
If there are plants which contain these chemicals and are
already used as human food or medicine, a monitoring study could
look for any effects of using such plants (together with whatever
other treatments each patient was already using) on p24 antigen
level, T-helper count, or other laboratory or clinical measure-
ments. Such a project would cost little, and could be conducted
by a community-based research organization.
*****
INTERFERON, HIV, AND KAPOSI'S SARCOMA UPDATE
by Denny Smith
Alpha interferon, approved by the Food and Drug Administra-
tion last November for the treatment of Kaposi's sarcoma (KS),
has received more attention lately as a treatment for HIV infec-
tion as well as AIDS-related KS. Interferons are naturally occur-
ring proteins secreted by cells in response to infection, and
they serve multiple roles as antiviral, antitumor, and immune
stimulating agents. The three major classes of interferon
(alpha, beta, and gamma) have been synthesized, and each is being
studied in various applications for the treatment of HIV and
AIDS.
A combination of alpha interferon and AZT was discussed as a
possible improvement in HIV antiviral therapy in the May 5 issue
of Science (Poli and others). The authors, reporting on the
results of in vitro research at the National Institute of Allergy
and Infectious Diseases (NIAID), found that alpha interferon
prevented the assembly and release of new virus from cells chron-
ically or latently infected with HIV, interrupting the progress
of HIV at a point later in the life of the virus than AZT, which
inhibits viral replication within infected cells. Combining the
two drugs would theoretically enhance, not just duplicate, their
anti-HIV potential.
(Note: For a different viewpoint on alpha interferon, see
recent article by Joseph Sonnabend, M. D., cited in references
section, below. Dr. Sonnabend, an interferon expert and a
cofounder of the Community Research Initiative in New York,
points out that alpha interferon levels are already too high in
many persons with AIDS, and that high levels might contribute to
the disease process.)
A small clinical trial involving asymptomatic seropositive
individuals, was discussed at the V International Conference on
AIDS in Montreal in June. In this study, 35 million units of
subcutaneous alpha interferon given daily for 12 weeks appeared
to slow the decline of helper cells and reduce the risk of
developing opportunistic infections (Lane and others). The
August 15 issue of Annals of Internal Medicine published addi-
tional findings from NIAID which further support the combined use
of AZT and alpha interferon to combat HIV infection and HIV-
associated KS. After comparing various pairings of AZT and alpha
interferon doses, the researchers found that the maximum dose of
both drugs which could be tolerated without serious side effects
was 100 mg of AZT every four hours with a single daily injection
of 5 to 10 million units of alpha interferon. This was enough to
obtain an antitumor and anti-HIV effect in some participants,
without an increase in the side effects normally seen separately
with higher-dose AZT or interferon. Unfortunately the combina-
tion produced some unexpected toxicities: decreased platelets
and neutrophils, and liver dysfunction. These generally occurred
at the larger AZT doses.
The researchers note that the antiviral and antitumor bene-
fits cannot for certain be attributable to the interferon/AZT
combination, rather than to interferon alone. But this combina-
tion has the advantage of confronting KS while inhibiting HIV at
two different steps in its replication; combined therapies are
often better than single-agent treatments. The pattern of these
studies is in line with others which found a correlation between
a decrease in alpha interferon levels and the depletion of helper
cells in HIV infection, suggesting the use of alpha interferon as
a marker for monitoring the activity of HIV as well as an agent
for blocking it (Rossol and others, 1989). High doses of alpha
interferon can cause unpleasant side effects; Dr. Mathilde Krim
of the American Foundation for AIDS Research, told The New York
Times (August 15) that alpha interferon should be tried early in
HIV disease, at low doses. Beta interferon is also being combined
with AZT in clinical studies, and we hope to report on that in
the near future.
In the treatment of KS, AZT has been studied in combination
with alpha interferon with more success than the combination of
alpha interferon and other chemotherapeutic agents, which seems
to increase toxicity more than benefits. In March 1989, the
Annals of Internal Medicine published a thorough overview of the
use of alpha interferon for KS, by Jerome E. Groopman, M. D. and
David T. Scadden, M. D. of New England Deaconess Hospital. Among
their observations, Drs. Groopman and Scadden noted that alpha
interferon's capacity to inhibit the proliferative growth of KS,
as well as its stimulation of the immune system's own antitumor
activity, may make it an attractive alternative to chemotherapy
agents like vincristine, vinblastine, doxorubicin, and bleomycin,
which can further impair immune functions with bone marrow toxi-
city. They pointed out that interferon worked much better when
patients had T-helper cell counts over 200.
We spoke with Dr. Scadden, who is now conducting a trial in
Boston involving the use of alpha interferon with AZT to treat
KS, with the addition as warranted of granulocyte macrophage-
colony stimulating factor (GM-CSF), a synthesized product of the
immune system which may reverse some of the toxicity of the com-
bination, and which has been speculated to potentiate its
activity. This is not a placebo trial. Interested people can
call 617/732-8528. Dr. Scadden cautioned that combining inter-
feron with AZT is still an experimental idea, and would be con-
sidered a long-range therapy even if it is successful. People
who need more immediate treatment for cosmetically or function-
ally impairing KS lesions would obtain a more short-term response
from conventional chemotherapy (see AIDS TREATMENT NEWS #73,
January 27, 1989).
AIDS TREATMENT NEWS #75 (March 10, 1989) also reported on
the use of alpha interferon, and on two other relatively new
therapies for KS -- laser surgery and the Prosorba column.
Although interferon has been usually described as a systemic
treatment which is administered by injection into muscle tissue
or beneath the skin surface, we recently heard of a physician
giving alpha interferon intralesionally -- that is, small amounts
injected directly into the edges of individual lesions. Ostensi-
bly there would be few systemic benefits from this administra-
tion, but neither would there be the disadvantage of unpleasant
side effects which often accompany the larger injections. Such
an approach might be appropriate for small lesions which are few
in number and do not need more aggressive treatment. (The offi-
cial indications for the administration of alpha interferon are
described on the product insert.)
Earlier, in issue #73, we described some standard chemoth-
erapy for KS, both intravenous and intralesional, and radiation
therapy. The ratio and frequency of the drugs described in that
article had been refined to minimize the side effects usually
seen with chemotherapy. The substances used in chemotherapy are
usually caustic and must be handled with plastic gloves by the
health care workers involved. Sometimes during the administra-
tion of intravenous medication, some of the I. V. fluid escapes
from the puncture site (extravasation) into surrounding tissues.
If the I. V. needle is withdrawn as soon as this is noticed, it
is not ordinarily a serious problem. However, in the case of
chemotherapeutic agents, it means that the surrounding tissue has
been exposed to a drug designed intentionally to kill cancerous
cells, and which can also have a corrosive effect on many healthy
cells.
The ulcer resulting from this mishap can take weeks or
months to heal, as well as make an important I. V. site unavail-
able. Several years ago researchers at the University of Alabama
discovered that butylated hydroxytoluene (BHT) greatly reduced
the progression of necrosis (dead and dying tissue) in
doxorubicin-induced skin ulcers in mice (Daugherty and others,
1985); they suggest its evaluation in modifying skin necrosis
from doxorubicin.
In addition to interferon, radiation, lasers, chemotherapy,
and the Prosorba column, other possible treatments for KS under
investigation include bropirimine ABPP, CL246,738, IMREG 1 and 2,
and interleukin II. Tumor necrosis factor (TNF) is a substance
naturally produced by macrophages and is active against a variety
of tumors, but a study at the University of California in Los
Angeles found multiple toxicities and no obvious antitumor or
anti-HIV effect with TNF administered intravenously (Aboulafia
and others, 1989). Another study at the University of California
San Francisco Medical Center obtained some reduction in lesion
size and number, but not without side effects, by administering
TNF intralesionally (Kahn and others, 1989). Finally,
cimetidine, a common prescription drug which has been shown to
have immune stimulating and antitumor properties, may be a com-
plementary treatment possibility for KS (see AIDS TREATMENT NEWS
#80). We will follow new treatments as they progress.
References
Aboulafia, D and others. Intravenous recombinant tumor necrosis
factor in the treatment of AIDS-related Kaposi's sarcoma. Jour-
nal of Acquired Immune Deficiency Syndromes, volume 2, number 1,
pages 54-58, 1989.
Daugherty, JP and Khurana, A. Amelioration of doxorubicin-
induced skin necrosis in mice by butylated hydroxytoluene. Cancer
Chemotherapy and Pharmacology, pages 243-246, Spring 1985.
Groopman, JE and Scadden, DT. Interferon therapy for Kaposi's
sarcoma associated with the acquired immunodeficiency syndrome
(AIDS). Annals of Internal Medicine, volume 110, number 5, pages
335-337, March 1, 1989.
Kahn, JO and others. Intralesional recombinant tumor necrosis
factor-alpha for AIDS-associated Kaposi's sarcoma: A randomized,
double-blind trial. Journal of Acquired Immune Deficiency Syn-
dromes, volume 2, number 3, pages 217-223, 1989.
Kovaks, JA and others. Combined zidovudine and interferon- alpha
therapy in patients with Kaposi's sarcoma and the acquired immu-
nodeficiency syndrome (AIDS). Annals of Internal Medicine,
volume 111, number 4, pages 280-287, August 15, 1989.
Poli, G and others. Interferon-alpha but not AZT suppresses HIV
expression in chronically infected cell lines. Science, volume
244, pages 575-577, May 5,1989.
Rossol, S and others. Interferon production in patients infected
with HIV-1. The Journal of Infectious Diseases, volume 159,
number 5, pages 815-821, May 1989.
Sonnabend, JA. Fact and speculation about the cause of AIDS.
AIDS Forum volume 2, number 1, pages 2-12, May 1989.
*****
THE NATIONAL AIDS UPDATE -- CONFERENCE OCTOBER 10-14 IN
SAN FRANCISCO
This major AIDS conference for healthcare professionals com-
bines four previous conferences: The National AIDS Conference,
AIDS/ARC Update, Comprehensive Care of the AIDS Patient, and
Management of the AIDS Patient in Hospital and Outpatient Set-
tings. Sponsors include the San Francisco Department of Health,
San Francisco General Hospital, and the U. S. Public Health Ser-
vice. Areas covered in the conference include education and
prevention, care and services, policy and administration, and
treatment.
Registration is $195.00 regular, $25.00 for persons with
AIDS or ARC.
For more information about The National AIDS Update, contact
Krebs Convention Management Services, 415/255-1297, or by fax at
415/255-8496.
*****
NEW YORK: PWA HEALTH GROUP PUBLIC FORUM, SEPTEMBER 27
The PWA Health Group, New York's well-known "buyers' club",
will hold its first annual public forum at 7:30 PM on Wednesday,
September 27. The organization will discuss its policies and
finances, and be open for questions by the public and the media.
This nonprofit group maintains a policy of full disclosure, and
urges other organizations to follow suit in order to maximize
accountability to their clients, people with AIDS.
The meeting will be held at the Lesbian and Gay Community
Services Center, 208 West 13th St., in New York City.
*****
SAN FRANCISCO: "MOTHER, MOTHER" BENEFIT FOR COMMUNITY RESEARCH
ALLIANCE, FAMILY LINK, SEPTEMBER 28
A benefit showing of the award-winning drama "Mother,
Mother," and a reception with the stars, will take place Thurs-
day, September 28 at the Palace of Fine Arts in San Francisco.
"Mother, Mother," exploring conflict and reconciliation in
the complex relationship between a young man with AIDS and his
mother, was produced for AIDS fundraising by the volunteer work
of over 300 people in the film industry. The San Francisco show-
ing will benefit the Community Research Alliance, which is con-
ducting community-based research on AIDS treatments, and Family
Link, which provides affordable, supportive accommodations for
families and friends visiting persons with AIDS or other life-
threatening diseases in San Francisco.
"Mother, Mother" is directed by Micki Dickoff; the cast
includes Polly Bergen, Bess Armstrong, John Dye, and Piper Lau-
rie, with music by Henry Mancini. It received the 1989 Gold
Angel for Best Short Feature of the Year.
The San Francisco reception with the stars will be at 6:00
PM; screening is at 7:30, and there may also be a later showing.
Tickets are $25 for the screening, $100 for reception and screen-
ing. For tickets or for more information, call 921-4469 or 626-
2145.
*****
AIDS TREATMENT NEWS COMING IN BOOK FORM
Celestial Arts in Berkeley, CA will publish AIDS TREATMENT
NEWS issues number 1-75 as a paperback book, including an
improved, extensive index. The retail price will be $12.95 (for
numbers 1 through 75), making the complete set of back issues
much less expensive than in the past. We hope to have the book
available in November, but cannot guarantee a date.
Anyone who wants to purchase the back issues at this time
should call AIDS TREATMENT NEWS, 415/255-0588 for price and avai-
lability information. We will publish a notice in the newsletter
as soon as the book is available.
*****
STATEMENT OF PURPOSE
AIDS TREATMENT NEWS reports on experimental and complementary
treatments, especially those available now. It collects informa-
tion from medical journals, and from interviews with scientists,
physicians, and other health practitioners, and persons with AIDS
or ARC.
Long-term survivors have usually tried many different treatments,
and found combinations which work for them. AIDS TREATMENT 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.
HOW TO SUBSCRIBE TO AIDS TREATMENT NEWS
Send $100.00 per year for 26 issues ($150.00 for businesses and
organizations), or $30.00 reduced rate for persons with AIDS or
ARC who cannot afford the regular rate, to: ATN Publications, P.
O. Box 411256, San Francisco, CA 94141. A six-month subscription
(13 issues) is $55.00 ($80.00 for businesses or organizations),
or $16.00 reduced rate. For subscription information and a sam-
ple issue, call 415/255-0588.
For the complete set of over 80 back issues, call AIDS TREATMENT
NEWS for information. The back issues include articles on DDI,
compound Q, fluconazole, AZT, aerosol pentamidine, ganciclovir
(DHPG), diclazuril, DHEA, lentinan, peptide T, passive immunoth-
erapy, and many other treatments.
To protect your privacy, we mail first class without mentioning
AIDS on the envelope, and we keep our subscriber list confiden-
tial.
Outside North America, add $20.00 per year for airmail postage,
and $18.00 airmail for back issues. Outside U. S. A., send U. S.
funds by International Postal Money Order, or by travelers
checks, or by drafts or checks on U. S. banks.
Copyright 1989 by John S. James. Permission granted for non-
commercial reproduction.
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