AIDSNEWS%RUTVM1.BITNET@oac.ucla.edu (AIDS/HIV News) (12/15/89)
AIDS TREATMENT NEWS, Issue #92, December 1, 1989
Contents:
NAC: New Information ddI Access Impeded; Protests Planned
December 14 Passive Immunotherapy: Patent Dispute Impedes
Research Passive Immunotherapy: Important Address Change New
York: Research Nurse Help Wanted Iscador: Promising Experience
to Date Survey: What to Use after AZT
NAC: NEW INFORMATION
by John S. James
On October 6, AIDS TREATMENT NEWS reported that a prescrip-
tion drug commonly used in Europe to treat bronchitis (N-
acetylcysteine, or NAC), might also be useful as an HIV treat-
ment. New information continues to suggest that NAC might be
valuable. While the drug is far from proven, the growing evi-
dence in its favor--as well as its relative safety and availabil-
ity, and the short time needed to see whether it is working--
suggest that this potential treatment belongs among the top
priorities of the AIDS community.
This article reviews a major academic study, published
December 2; the study did not directly involve NAC, but it con-
firmed the existence (in symptom-free persons with HIV) of the
serious biochemical defect which this drug has been found to
treat. In addition, we interviewed an activist in Florida who
has followed 24 people who are using NAC; he told us that all of
them seemed to benefit.
Background
Use of NAC for HIV infection was first suggested by a German
immunologist, Dr. Wulf Droge. Dr. Droge knew that levels of a
chemical called glutathione were abnormally low in persons with
AIDS; these levels fell further as the disease progressed. He
also knew that NAC increased glutathione levels to normal or
almost normal values (within a few hours in the two HIV- positive
people who tried the drug), and that proper glutathione levels
are important for immune functions and for other reasons.
In October 1988, Dr. Droge sent a cover letter and unpub-
lished manuscript to colleagues in various countries, urging that
they give appropriate attention to this information, which "may
be life-saving or life-prolonging for many AIDS patients." The
manuscript had been submitted to Nature; it was later published,
but in a journal not well known to U. S. AIDS researchers or phy-
sicians (Eck and others, 1989). The cover letter had pointed out
that pharmaceutical companies were unlikely to pursue NAC aggres-
sively, because it was already widely available and would be dif-
ficult to protect by patent.
NAC first came to public attention in October, 1989, after
news reports that two professors of genetics at Stanford Univer-
sity (Dr. Leonard Herzenberg and Dr. Leonore Herzenberg) told a
scientific conference in Geneva of laboratory results suggesting
that the drug might inhibit the AIDS virus. At that time we also
reported that at least ten people were using NAC as an HIV treat-
ment, apparently with good results.
In the United States, NAC has been available only in an
aerosol form, which is not suitable for oral use for treating
HIV. Buyers clubs are now beginning to obtain oral forms of the
drug.
(For more background information, see "NAC: Bronchitis Drug
May Slow AIDS Virus," AIDS TREATMENT NEWS #88, October 6, 1989.)
New Scientific Study: Glutathione Deficiency Confirmed
A study by seven researchers at the National Heart, Lung,
and Blood Institute of the U. S. National Institutes of Health,
and an eighth at Universitaire Sherbrooke, Quebec, was published
in The Lancet, December 2, 1989 (Buhl and others, 1989). The
researchers reported that glutathione levels in blood plasma of
symptom-free HIV-positive subjects were found to be only 30 per-
cent of those of uninfected controls. (The 14 HIV-positive sub-
jects, all symptom-free, had an average T-helper count of 346;
four were taking AZT and the other ten were untreated.) Fluid
from the lungs, obtained by bronchoalveolar lavage, was also
tested for glutathione, and persons with HIV were found to have
60 percent of normal levels.
The paper listed many important functions of glutathione.
It is believed to protect cells from oxidation injury, aid in
synthesis of proteins and DNA precursors, and serve as a cofactor
for certain enzymes. It also has direct effects on the immune
system:
"Glutathione is also believed to be important in the initia-
tion and progression of lymphocyte activation, and thus essential
for host defense. Furthermore, depletion of intracellular glu-
tathione inhibits lymphocyte activation by mitogens, and glu-
tathione is critical for the function of natural killer cells and
for lymphocyte-mediated cytotoxicity."
In short, this paper confirms and extends the pioneering
work of Droge, two of whose papers are cited in its references.
On December 1, The New York Times published an article on
this work ("New Research Suggests Underlying Factor in AIDS"),
and interviewed one of the researchers, Dr. Ronald G. Crystal.
According to the Times article, the researchers have developed an
aerosolized glutathione (not NAC) to spray directly into the
lungs to see if it will correct the deficiency there. Several
months will be required just to find the right dose of this chem-
ical.
Question
Why develop a new drug to restore glutathione levels only in
the lungs, when NAC has already been found to do so systemically?
We could not reach the researchers by press time to answer this
question. Another scientist familiar with the subject pointed
out that this research team consists of pulmonary specialists and
experts in aerosol medication; their interest is studies of the
lungs. The paper seems to go out of its way to avoid mentioning
NAC, especially in the short section at the end where less
promising methods of raising glutathione levels are discussed.
The Florida Study
The Fight for Life Committee, an AIDS activist organization
in North Lauderdale, FL, is collecting information from 24 people
who are using NAC as an HIV treatment. (The Fight for Life Com-
mittee is described by chairman Lenny Kaplan as a "Southern-style
ACT UP"--one which works through court challenges and the media
more than through demonstrations. For example, the organization
has successfully gone to court to obtain AZT for prisoners with
AIDS. It is also working through the state legislature and oth-
erwise to reduce the cost of aerosol pentamidine treatment in
local hospitals.)
When we interviewed Mr. Kaplan on December 3, the 24 people
had used NAC for between 10 and 45 days. All of them are keeping
diaries. All of them have ARC or AIDS. Interpretation of
results is complicated by the fact that 12 of the 24 are also
using Compound Q; but those involved attribute the following
benefits and side effects to NAC. (Mr. Kaplan told us that the
NAC seemed to work better and sooner for those who had also used
compound Q; he felt there should definitely be a clinical trial
to test the combination.)
Everybody reported increased energy, often greatly
increased; persons who once needed naps during the day have
become able to work full time without them. Only a few have
blood work results available after using NAC; their T-helper
counts were up by an average of about 75.
The two who showed the most benefit both had wasting syn-
drome. One gained 12 pounds, and his physician found no new
growth of KS. The other gained 10 pounds.
Some people had headache or dizziness during the first week.
The dose had to be reduced to 1000 mg per day (500 mg after
breakfast and 500 mg after dinner) after three of the first five
had stomach upset on a higher dose. These side effects may have
been due to the formulation of the drug (see below).
For more information about the NAC study or about The Fight
for Life Committee, call Lenny Kaplan, 305/566-6753. Donations
are needed. Fight for Life is planning a conference on AIDS
treatments in Ft. Lauderdale on February 2 and 3; for informa-
tion, call the number above.
Drug Formulation Issues
Many brands of NAC are sold in different countries in Europe
for oral use. As far as is known, any of these brands would be
satisfactory; however, most contain large amounts of sugar or
other sweeteners to cover the bad taste of the NAC; some patients
might not want the sweeteners. Prices vary as much as 3-fold
between expensive countries (such as Germany or England) and
inexpensive countries (such as Spain). Persons with HIV are
using somewhat more of the medication than persons with bron-
chitis; as a result, NAC costs about $2. per day even from the
less expensive countries, with doses of 1600 mg per day (400 four
times per day) or 1800 mg per day (600 three times).
Meanwhile, the chemical NAC has been pressed into tablets
and sold at prices much less than the European brands. Because
these tablets are not regulated as drugs, there is widespread
concern that they might not be safe. Some of the concerns we
have heard are:
* Customers can only trust that the manufacturer used a
grade of the chemical intended for human use;
* According to one chemist, the European products are packed
in foil because they oxidize rapidly when exposed to air. The
other tablets are just put into bottles. They may have a short
shelf life, especially after the bottles have been opened. The
shelf life needs to be checked.
* All or almost all of the European brands are intended to
be dissolved in water outside the body before being taken. Usu-
ally the drug is provided as a single-dose packet of powder.
These packets are not as convenient as pills, especially since
NAC has an unpleasant taste; presumably the packets are provided
for a reason, possibly to reduce stomach irritation.
To avoid such problems, the PWA Health Group in New York is
planning to obtain one of the European NAC preparations. For
more information, call them at 212/532-0280. The PWA Health
Group is also planning to do its own chemical testing and other
research on the suitability of the various formulations.
It may be possible to create a very inexpensive product
which is satisfactory--perhaps by putting pharmaceutical-grade
NAC into capsules to be opened before use, and dissolved in
water. Some research--for example, checking with pharmacologists
in Europe--would be necessary.
There are efforts to organize a formal clinical trial of NAC
as an HIV treatment. These efforts are moving slowly, and it
will probably be years before the drug is officially approved.
NAC is not a high priority for any organization. Meanwhile the
AIDS community must organize itself to obtain proper supplies,
and to collect the best information possible about this potential
treatment and its uses.
References
Buhl, R. and others. Systemic glutathione Deficiency in
Symptom-Free HIV-Seropositive Individuals. The Lancet, pages
1294-1297, December 2, 1989.
Droge, W and others. Glutathione augments the activation of
cytotoxic T lymphocytes in vivo. Immunobiology, volume 172
number 1-2, pages 151-156, August 1986.
Eck, HP and others. Low concentrations of acid-soluble thiol
(cysteine) in the blood plasma of HIV-1 infected patients. Biol
Chem Hoppe Seyler, volume 370 number 2, pages 101-108, February
1989.
ddI ACCESS IMPEDED; PROTESTS PLANNED DECEMBER 14
by John S. James, December 6
New restrictions on access to the antiviral ddI, imposed
under pressure from Federally-funded principal investigators
(PIs) in the AIDS Clinical Trial Group (ACTG) system, are leading
to a bitter dispute over patients' access to experimental treat-
ments. The PIs say that allowing patients to use ddI outside of
formal trials is harming their research, by making it difficult
to recruit subjects. Patient advocates say that the recruiting
difficulties are not due to the expanded access, but to poor
design and administration of the trials.
We do not know how many of the PIs oppose expanded access.
But it is clear that many have strongly fought against Fauci's
"parallel track" proposal, against the current system of expanded
access to ddI under existing regulations (technically different
from "parallel track," which has not yet been officially
defined), and also against the FDA's liberalized rules for
patients seeking medicines approved abroad for personal use. In
short, some of the PIs have consistently fought against patients'
access to treatment options--both openly, and (more importantly)
behind the scenes--on the grounds that if patients have more
options, they will not volunteer for their studies.
Now some patients requesting ddI are unexpectedly being
denied it, and there is widespread suspicion that pressure from
PIs is to blame. For example, Bristol-Myers was expected to drop
the requirement for an AIDS diagnosis for access to ddI by
patients who are failing AZT, allowing patients otherwise quali-
fied to enter this program even if technically they only have
ARC. Now it appears that this restriction will not be dropped,
although exceptions might be considered on a case-by- case basis.
We are also hearing reports of a general slowdown in the system,
with patients who are eligible under all the rules being told
that there is not enough drug--when before we had heard that
there was no problem with supply.
Arguments against allowing wider use of the drug were stated
in a much-criticized article on page 1 of The New York Times,
November 21, 1989. Headlined "Innovative AIDS Drug Plan May Be
Undermining Testing," this article reported that "almost 20 times
as many people have flocked to free distributions of the new drug
ddI than have signed up for the clinical trial, leaving research-
ers in despair over whether they will ever be able to complete
the formal study." But with a closer look shows a very different
picture:
* According to Bristol-Myers, available data on the patients
who have "flocked" to ddI distribution outside of the trials show
that 60 percent of them would not be allowed into any of the
three ddI trials because they do not meet medical criteria, and
another 30 percent live too far from the nearest trial site to
participate. Well under 10 percent could possibly have entered a
formal study.
Some principal investigators have dismissed these numbers by
saying that doctors lie to get ddI for their patients, and there-
fore some of those counted as ineligible for the formal studies
may really have been eligible. But they have not presented any
evidence to show whether significant number of patients are lost
to the study this way.
* At some of the sites where the study will be conducted, no
one can enroll because the local institution is not ready for
them. Often the local Institutional Review Board has not yet
given its approval. The program to allow expanded access to ddI
to patients ineligible for the trials cannot be blamed if low
enrollment totals result from the fact that some centers are not
ready.
* Some of the study sites only have enough staff to enroll a
few patients a week.
For these and for other reasons, patients are on waiting
lists at some of the centers--in some cases, for months. And
most centers have done little or nothing to tell the public about
their studies.
* In addition, there are concerns about the studies them-
selves. In two of the them, patients may be randomized to 1200 mg
of AZT per day--the dose which is officially approved but which
the medical community is rapidly coming to consider too high.
Attempts to change the trial to use a lower dose have not yet
succeeded. Other concerns include the appropriateness of random-
izing patients to AZT when those patients were selected to be
ones for whom that drug is likely to be losing effectiveness
(study number ACTG 117). Such concerns about study design create
disincentives for patients to enroll.
* Despite all these problems, the ddI studies have actually
recruited faster than most ACTG trials in the past (when there
was no system for access outside of trials), according to Jim
Eigo of ACT UP/New York, who for months has been one of the prin-
cipal patient advocates in the ddI negotiations.
Demonstration December 14
ACT UP/New York is planning protests on December 14 against
denial of treatment to patients who have no other alternatives.
Protests are also being planned in other cities. These demons-
trations are being called on very short notice. For more infor-
mation, ask ACT UP/New York at 212/989-1114, or call David Barr
at Lambda Legal Defense and Education Fund, 212/995-8585.
If You Have Trouble Getting ddI
David Barr of Lambda Legal is collecting information about
peoples' experiences when they try to obtain ddI, either by
volunteering for a trial or by trying to enter the expanded
access program. Anyone who has difficulty should call him at the
above number. Many of the access problems have not been
announced, but have been discovered by comparing notes of persons
who have been turned down.
For More Information
For more information about the controversy over access to
ddI, see the column by Mark Harrington and letter by Jim Eigo in
Out Week magazine (New York, December 10 issue date). There is
also an unpublished November 21 letter to The New York Times from
David Barr and Jay Lipner of Lambda Legal, and a November 21
press statement by Project Inform, both written in response to
The New York Times article of that date.
PASSIVE IMMUNOTHERAPY: PATENT DISPUTE IMPEDES RESEARCH
by John S. James
An important study of passive immunotherapy by Marcus
Conant, M. D. in San Francisco may be halted by a patent dispute
between two rival companies. Recently Medicorp, of Montreal,
Quebec, obtained a broadly-worded patent for passive
immunotherapy--a treatment consisting of plasma transfusions from
selected donors with high levels of anti-HIV antibodies, to reci-
pients who need the antibodies. In a November 28 letter from its
attorneys, Medicorp refused a request from Immutech, a small
Solano Beach, CA company working with Dr. Conant, for permission
to use passive immunotherapy. After months of preparation, Dr.
Conant had obtained California approval and was ready to begin
the trial, designed to treat 40 people, some who are very sick.
There is no placebo arm in this study.
AIDS activists are considering a legal challenge to the
patent through the patent office. They may also prepare a wrong-
ful death lawsuit, to be brought against Medicorp if anyone dies
while waiting for treatment.
For more information, see the letter from Jesse Dobson of
ACT UP/San Francisco, published in The San Francisco Bay Times,
December 1.
PASSIVE IMMUNOTHERAPY: IMPORTANT ADDRESS CHANGE
The PATH Project, the San Francisco area branch of the Pas-
sive Immunotherapy Foundation, has a new address and phone
number. Readers should change any old address in their files,
because due to a postal regulation, mail will not be forwarded
from the old address after this month. The new mailing address
is: PATH Project, 1748 Market St., San Francisco, CA 94102,
phone 415/626-8455.
The Passive Immunotherapy Foundation, a nonprofit group
started by patients, publishes a newsletter and is planning a
clinical trial to begin in 1990. For more information, contact
the PATH Project at the address or phone number above.
NEW YORK: RESEARCH NURSE HELP WANTED
The Community Research Initiative in New York has an opens
for a Director of Clinical Nursing, and for Clinical Research
Nurses. For more information, contact the Community Research
Initiative, 31 West 26th St., New York, NY 10010, 212/481- 1050.
ISCADOR: PROMISING EXPERIENCE TO DATE
by Denny Smith
An extract from mistletoe which has been used for more than
sixty years in Europe to treat certain solid-tumor cancers has
been studied in the U. S. recently for immunomodulatory and
anti-viral activity against HIV. Viscum album, or European
Mistletoe, is the species from which an aqueous extract is pro-
duced by the Institut Hiscia in Switzerland, under the trade name
Iscador.
The most extensive HIV-related clinical work with Iscador
has been conducted by two physicians in San Francisco; both are
European-educated. Immaculada Marti, M. D., from Spain, is a
staff physician at Davies Hospital in San Francisco, and treats
many people with HIV in her practice. Robert Gorter, M. D. from
The Netherlands, is an Associate Professor at the University of
California in San Francisco.
We asked Dr. Marti to share her impressions of Iscador's
usefulness. Although her experience, and Dr. Gorter's as well,
has been encouraging, she feels that it cannot be described as
conclusive. The last report of their work appeared a year ago,
in the November '88 issue of BETA, a treatment bulletin of the
San Francisco AIDS Foundation.
At least thirty seven different components have been iso-
lated from Viscum album, characterized as polysaccharides, visco-
toxins and lectins. The latter two are under study for anti-
tumor and immunomodulatory properties. Iscador is available in
two preparations: the useful lectins are preserved in unfer-
mented extract of Viscum album, while the fermented version loses
an important lectin. As a semi-parasitic organism, mistletoe
requires life on a host plant, often apple, oak, elm, or pine
trees. Interestingly, the chemical properties of the parasite
plant vary somewhat depending on which host tree it grows.
Dr. Taseem A. Khwaja, Director of the Comprehensive Cancer
Research Center of the University of Southern California has
observed that Iscador blocks in vitro syncytia formation, the
clumping of cells which provides HIV an efficient passage from
cell to cell. He suggests that Iscador may also inhibit the
binding of free virus to the receptors of uninfected cells, as
well as inhibit reverse transcriptase within infected cells. In
spite of its apparent potential, Viscum album actually demon-
strates little ability to directly harm HIV particles, but Dr.
Khwaja is investigating another species of mistletoe, Viscum
coloratum, which may be superior in this regard.
In her clinical experience, Dr. Marti has seen Iscador
enhancement of five specific immune responses:
* An increase in the number and activity of neutrophils;
* Increase in T4-helper cells;
* Increased number and activity of Natural Killer cells;
* Enhanced anti-body dependant cell-mediated cytotoxicity
(ADCC);
* Increased lymphocyte mitogenicity, or immune cell- multi-
plication.
Some of these responses are similar to those obtained with
alpha interferon treatments, and in fact Iscador appears to
facilitate the immune system's own production of interferon.
Related improvements in Dr. Marti's patients included weight
gain, reduction of KS lesions, decreased lymphadenopathy,
increased hemoglobin, and decreases in beta 2 microglobulin and
p24 antigenemia. She notes, however, that the positive KS
response does not appear to result directly from the effect of
Viscum album on KS lesions, but rather from an indirect enhance-
ment of the body's immune response to KS.
Iscador is administered by subcutaneous injection two or
three times a week, beginning with a low dose, 0.01 mg. As it is
presently formulated, Iscador is less effective taken orally,
since some components are inactivated in the gastrointestinal
tract. The dosage is gradually increased, and doses approaching
15 to 20 mg resulted in blood work improvements for asymptomatic
patients. However, people who are currently fighting an oppor-
tunistic infection or who have low helper cell counts seem to
have a lower dose tolerance, above which the drug may become use-
less or detrimental. So the dosage must be tailored depending on
these factors. (A similar observation was made in the results of
Project Inform's recent study of Compound Q.) Many people
experience redness and tenderness at the injection site, but no
serious or permanent toxicity has been attributed to Iscador.
Reactions in some people to high doses caused fever, insomnia,
fatigue and loss of appetite. Temporarily discontinuing the
injections resolved the reaction.
No other medications are contraindicated with the use of
Iscador, and in fact Dr. Marti has combined it successfully with
AZT, chemotherapy and ddI. She has found that Iscador helps
counter the bone marrow suppression induced by long-term use of
AZT. In addition to the objective improvements in blood markers,
her patients have reported improved appetite and sleep, vivid
dreams, and relief from HIV-associated fatigue and depression.
All of these observations would seem to make Iscador, or
some future Viscum preparation, a very pursuable treatment possi-
bility. As a prescription drug in Switzerland, Iscador costs
about $4 an ampule, or $12 a week, and personal use requests can
be sent with a physician's prescription directly to the manufac-
turer: Institut Hiscia, CH-4144 Arlesheim, Kirschweg 9, Switzer-
land. Drs. Gorter and Marti continue to monitor their patients'
response to Iscador, and are interested in conducting formal tri-
als to expand their study.
(For more information about Iscador in HIV treatment, physi-
cians can call Dr. Marti at 415/255-7941.)
References
Holtskog, R and others. Characterization of a toxic lectin in
Iscador, a mistletoe preparation with alleged cancerostatic pro-
perties. Oncology, volume 45, number 3, pages 172-179, 1988.
Kuttan, G and others. Isolation and identification of a tumor
reducing component from mistletoe extract (Iscador). Cancer
Letters, volume 41, number3, pages 307-314, 1988.
Hamprecht, K and others. Mediation of human NK-activity by com-
ponents in extracts of Viscum album. International Journal of
Immunopharmacology, volume 9, number 2, pages 199-209, 1987.
Metzner, G and others. Effects of lectin I from mistletoe (ML I)
and its isolated A and B chains on human mononuclear cells: mito-
genic activity and lymphokine release. Pharmazie, volume 42,
number 5, pages 337-340, 1987.
Oncology, (entire issue devoted to Viscum album) supplement 1 of
volume 43, 1986.
SURVEY: WHAT TO USE AFTER AZT
If you have used AZT for a total of a year or more (any
dose), you can help with this survey. Results will be reported
in AIDS TREATMENT NEWS. Your response must be mailed by January
15 to guarantee that it can be included.
Purpose: AZT is believed to become less effective after
about a year or more of use. We have heard anecdotal reports of
people apparently extending the usefulness of AZT by adding other
treatments to it, after the AZT had begun to lose effectiveness.
But we have not heard enough reports for any pattern to emerge.
We want to hear of anything you have done to extend the use-
fulness or improve the effectiveness of AZT, or to replace it--
whether the other treatment worked or not. Whether the new treat-
ment was used concurrently with AZT, used instead of AZT, or used
in alternation, we are interested.
It is OK to use the back of this form, or to use other
sheets of paper if necessary.
By helping us collect this information, you can help others
who are making the same decision.
I. After using AZT for a year or more, have you noticed any
apparent decline in its effectiveness? Mention any symptoms or
lab values which you believe are relevant. Also, let us know if
there have been any important, recent changes in AZT toxicity.
II. When did you first use AZT (month)? _______ What dose?
_______. If you have changed the dose, please give approximate
starting and stopping dates of each dose.
III. What treatment or combination of treatments have you started
to extend, improve, or replace AZT? (Include treatments started
before one year of AZT use.) Tell us how long in months you have
been using each treatment.
IV. Has the treatment or combination of treatments been success-
ful (yes, no, or unsure)? _______
V. What improvements (or lack of improvements) in symptoms or
laboratory tests support your answer to the question above?
VI. Tell us anything else we should know.
VII. Optional: If we can contact you in case we have any further
questions, please give us your name and phone number:
Please return to: Survey, ATN Publications, P. O. Box 411256,
San Francisco, CA 94141. Survey must be mailed by January 15 to
make sure it is included in our first report.
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.
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To order back issues, send $18.00 for issues #1 through #75, plus
the per-issue cost for each later issue you need. The per- issue
cost is $1.00 reduced rate, $2.00 individual or nonprofit rate,
and $4.00 for businesses and institutions Issues #1 through #75
are out of print and will be backordered until they are available
in the new paperback book. We will mail the more recent issues
immediately and send the book when it is available, sending both
by first-class mail. (Note that issues 1 through 75 will also be
available in bookstores, at a retail price of $12.95.) The back
issues include articles on DDI, compound Q, fluconazole, AZT,
aerosol pentamidine, ganciclovir (DHPG), diclazuril, DHEA, len-
tinan, peptide T, passive immunotherapy, hypericin, and many
other treatments.
Outside North America, add $20.00 per year for airmail postage,
$6.00 airmail for back issues #1 through #75, and $.50 for each
additional issue. Outside U. S. A., send U. S. funds by interna-
tional postal money order, or by travelers checks, or by drafts
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To protect your privacy, we mail first class without mentioning
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tial.
Copyright 1989 by John S. James. Permission granted for non-
commercial reproduction.