info-aids%pasteur.Berkeley.EDU@ucbvax.Berkeley.EDU (INFO-AIDS MAILER) (10/16/89)
AIDS TREATMENT NEWS Issue Number 88, October 6, 1989
CONTENTS: [items are separated by "*****" for this display]
NAC: Bronchitis Drug May Slow AIDS Virus
DDI Trials, Access Announced
"Compound Q" Results Released
Hypericin Note
PML Treatment Update
Buyers' Club Imports Low-Cost Aerosol Pentamidine
No Issue Published September 22
*****
NAC: BRONCHITIS DRUG MAY SLOW AIDS VIRUS
by John S. James
Stanford University researchers reported last week that a
drug widely used in Europe to treat bronchitis inhibits HIV in
laboratory tests. They are developing plans for clinical trials
of the drug, called n-acetylcysteine (NAC). No human results for
AIDS/HIV have been published, but AIDS TREATMENT NEWS has learned
that at least ten people are using NAC for this purpose, at least
one of them for almost a year.
Dr. Leonard Herzenberg and Dr. Leonore Herzenberg, who are
husband and wife and both professors of genetics at Stanford
University and well known for developing the Fluorescence-
Activated Cell Sorter (FACS), a machine widely used to count T-
cells, conducted the laboratory studies, together with other
researchers at Stanford. Last week Dr. Leonard Herzenberg
reported on their work with NAC at a scientific conference in
Geneva, Switzerland. The Herzenbergs credited a German immunolo-
gist, Dr. Wulf Droge at the German Cancer Research Center in
Heidelberg, for first suggesting the potential use of the drug in
AIDS.
In laboratory experiments, NAC increased the level of the
chemical glutathione in HIV-infected blood cells. Glutathione is
necessary for life, as it is needed for energy generation and
other cell functions. It also protects cells against oxidizing
agents. Dr. Droge had discovered that glutathione levels were
too low in persons with AIDS, and fell as the disease progressed.
He also knew that NAC had increased these levels when it was used
to treat bronchitis.
NAC is also believed to counter some effects of excessive
levels of tumor necrosis factor (TNF), which often occur in AIDS.
TNF is believed to increase the production of HIV, to cause wast-
ing syndrome in some cases, and to cause production of more TNF.
(Paradoxically, other reseachers are testing TNF as part of a
combination treatment for KS.)
The Herzenbergs' laboratory at Stanford is supported by the
U. S. National Institutes of Health. The NAC research received
support from the Zambon Group of Italy, which markets the drug.
In a Stanford University press release, the Herzenbergs
stressed that NAC is not a cure for AIDS, but that laboratory
results suggest that it might be a useful treatment. "Our stu-
dies show we can block the TNF activation of HIV with increased
thiol levels in models of HIV-infected cells. We propose that by
administering NAC we can augment thiol levels, and neutralize TNF
activity and production which will slow or stop the virus from
going into an active stage."
Comment
AIDS drugs are usually classified either as antivirals or as
immune modulators. NAC appears to be an antiviral, but it may be
better to consider it an example of a third class of potential
treatments--those which intervene in the pathogenesis of AIDS.
Pathogenesis has been defined as "the origin and development
of a disease." In AIDS research, a remarkable ignorance of
pathogenesis has been widely tolerated, probably because of an
unbalanced research focus on HIV and the search for a magic bul-
let to kill it. NAC appears to work (if it does) not by killing
the virus directly, but rather by correcting biochemical imbal-
ances which occur in the course of the illness, and which then
cause other problems, including further viral growth.
Human Experience with HIV
We interviewed one person who is using NAC, and several oth-
ers familiar with the drug or with the laboratory results sug-
gesting its possible use as an HIV treatment. This is what we
learned:
* At least ten people have tried NAC, and no side effects
have been reported. (The drug is generally considered very safe
in its standard use, treating bronchitis and other lung problems
by reducing the thickness of mucus. However, there is little
experience with long-term use by persons with AIDS.)
* Those most likely to benefit seem to be persons with
cachexia (wasting syndrome). Early reports are that these
patients feel better quite quickly, and then regain weight.
* Two persons with KS are using the drug. Both are said to
be doing well, but we do not have detailed information.
* There are also reports of improvement in T-helper cells
and p24 antigen levels. However, we do not have any detailed
information at this time.
* Almost everyone who has started the drug is continuing on
it, as they believe it is helping.
Availability
NAC for oral use is available in most of the world, but not
in the United States. It usually requires a prescription, but it
might be sold over the counter in some countries; we could not
find out by press time.
In the U. S., NAC is available only in a liquid form
intended for aerosol, not oral use. The liquid can be diluted
and given orally- -and is FDA-approved for such use, for treat-
ment of poisoning caused by overdose of acetaminophen, the paink-
iller in Tylenol and some other over-the-counter medicines. But
it would be difficult to use this liquid as an HIV treatment.
This formulation was not made for oral use, and often causes vom-
iting; many patients have trouble keeping it down. As an HIV
treatment, the drug would have to be taken three or four times a
day indefinitely.
Most people so far who have tried this drug for HIV have
used a brand named Fluimucil, which is available in Italy,
Switzerland, Germany, The Netherlands, and Spain, and perhaps
elsewhere. One person who has used it told us that Fluimucil
comes in two forms; an effervescent tablet containing 600 mg, and
a packet of powder with 200 mg. Both forms need to be dissolved
in a glass of water or fruit juice (not milk or hot drinks)
before being taken. NAC should not be heated above body tempera-
ture. The drug will not keep after it has been dissolved, so it
has to be mixed shortly before use, not stored and taken later.
Most people have taken 600 mg (one tablet) three times a day, or
400 mg four times a day, using the packets of powder. We have
heard that the drug is inexpensive in Europe.
There is much concern that in the U. S., where NAC for oral
use is not available, people will use chemicals not intended for
human consumption, resulting in unknown risks. To prevent this
from happening, some way of obtaining the pharmaceutical products
(through buyers' clubs or otherwise) will need to be set up.
There is also concern that people who try this drug may stop
taking other treatments. NAC is not a substitute for any other
drug. There are no known harmful interactions with other drugs
commonly used in treating AIDS; however one medical reference
warns that "some antibiotics including amphotericin, ampicillin
sodium, erythromycin lactobionate, and some tetracyclines are
either physically incompatible with or may be inactivated on mix-
ture with acetylcysteine (NAC)."
It is too early to tell if NAC will be useful. But cer-
tainly it is important to find out quickly. It is easy to call
for controlled clinical trials, and of course such trials are
necessary. The problem, however, is that there seems to be no
way for the drug to become available quickly through trials in
the United States (elsewhere it is already available). NAC has
been discussed among scientists as a potential AIDS treatment for
over a year; six months ago a protocol for a trial had been writ-
ten. The new attention resulting from recent public knowledge
about the drug may help to speed the process.
AIDS TREATMENT NEWS
Seeks Information
If you have any information about use of NAC for AIDS or
HIV, we would appreciate it if you would contact AIDS TREATMENT
NEWS at the above address or phone 415/255-0836 (or fax at
415/255-4659). We will, of course, keep your identity confiden-
tial.
Persons planning to start taking NAC should get blood work
done first--including T-cell counts and p24 antigen level--and
also record their weight, so that later they can tell whether or
not these measures improved after treatment. Asymptomatic
patients, in particular, will have no other way to judge whether
the drug is working for them.
Disclaimer
This article is not intended as instructions for using NAC.
It may omit necessary information; for example, we have not yet
seen the European product literature or instructions for physi-
cians, nor have we talked to U. S. physicians whose patients have
used the drug. Information for HIV-positive persons and their
physicians on how to use NAC still needs to be prepared.
*****
DDI TRIALS, ACCESS ANNOUNCED
by John S. James
On September 28 the U. S. Department of Health and Human
Services announced that the antiviral DDI would be tested in
three clinical trials, and also be made available to some people
who have no other option and cannot participate in the trials.
There has been some confusion as the details of this important,
urgent, and flawed program are worked out. This article reports
what we have learned about the present status of DDI; there will
be changes, probably for the better, in the future.
Background
DDI is an antiviral in the same class as AZT. Early human
trials suggest that it will probably be about as effective as
AZT, perhaps somewhat less. The immediate importance of DDI is
that it provides a different treatment option which may be effec-
tive when AZT is not. Persons who cannot tolerate AZT will prob-
ably be able to use DDI. And persons for whom AZT has stopped
working (probably because the AIDS virus has become resistant to
the drug) will probably also be able to benefit. Virus which has
become resistant to AZT is usually not resistant to DDI.
This drug is no cure. Like AZT, it must be taken indefin-
itely, and it has toxicities which limit the dose which can be
used. (They are different from AZT toxicities, however.) DDI
might also lose its effectiveness in many patients after a year
or two--it is too early to tell. For these reasons, persons who
are now using AZT successfully will probably want to stay with
what is working for them, and not start DDI until they need it,
or until more has been learned about it.
The new DDI program consists of three different formal clin-
ical trials, plus two other studies intended primarily to make
DDI available to some persons who cannot join the trials. Per-
sons not eligible for some of these programs might be eligible
for others.
In the discussion below, we include the most important (but
not all) of the inclusion and exclusion criteria--the details of
who can or cannot qualify to get DDI. Patients can get some sense
from this article of whether and how they might qualify. But we
did not include all the rules, because they are long and confus-
ing and might change in the future.
Some patients--and certainly any physicians who want to get
DDI for their patients--will want to obtain a current copy of the
full inclusion and exclusion criteria. Physicians will probably
receive a copy when they register with Bristol-Myers for the DDI
program (see phone number below); patients can probably receive a
copy from the Clinical Trials Information Service, a hotline on
clinical trials run by the U. S. Public Health Service; call
800/TRIALS-A. It is likely that various AIDS organizations will
also have copies. (This hotline, incidentally, can provide
information about clinical trials of DDI, as well as other exper-
imental AIDS drugs, in your area.)
As we show below, the current rules for access to DDI are
much too restrictive. Hundreds if not thousands of people will
be denied the treatment when they have no other alternative. To
prevent rejection, either patients and/or their physicians must
know the rules, in order to direct each patient to the right pro-
gram, put his or her best case forward, and submit an application
likely to be successful.
The Three Trials
The three trials starting now or expected to start soon will
compare DDI with AZT in two different groups of patients, and
also compare different doses of DDI in patients intolerant to
AZT. These trials are:
* ACTG 116--comparing DDI with AZT in patients with AIDS or
advanced ARC.
To be accepted for this trial, patients must be ages 12
through 99, and have either an AIDS diagnosis, or under 300 T-
helper cells and one of a number of ARC symptoms. They may have
taken AZT already; for the "116" study they cannot have used it
more than 48 weeks (but those who have used AZT for over a year
may qualify for ACTG 117, described below). If they have used
AZT, they must have been able to take at least 500 mg per day (a
low dose) without major intolerance.
Those who have taken AZT for over eight weeks and have ARC
must have met the entry criteria (under 300 T-helper cells and
one or more of certain symptoms) when they started AZT, but not
necessarily when they enter the study. But those who have taken
AZT for eight weeks or less can only enter the study with an AIDS
diagnosis, which must be due only to a single instance of PCP;
they cannot enter the study if they only have ARC. (Presumably
persons with ARC who are otherwise qualified could keep taking
AZT until the eight weeks are up, and then apply.)
There are many other exclusion criteria, such as KS requir-
ing chemotherapy, grade 2 neuropathy, past or present heart
disease, seizures within the last six months, certain liver
enzymes more than five times normal, or hemoglobin, neutrophils,
or platelets too low. A few prior or concurrent medications are
not allowed. Patients should check with their physicians, or
obtain a copy of the full criteria as described above. The entry
criteria we listed above are the ones likely to affect the most
people.
Fifteen hundred patients will be enrolled in this trial.
For those receiving DDI we do not know the dose, but it will
probably be 375 mg or less taken twice per day. Neither the
patients nor their physicians will be told which drug they are
getting.
All persons in this trial must be on aerosol pentamidine,
and they can use most other treatments for opportunistic infec-
tions as required, without being dropped from the study. We do
not know who will pay for the required aerosol pentamidine.
ACTG 116 will take place at about 50 different sites in the
U. S. Persons can call 800/TRIALS-A to find out if one is located
in their area.
* ACTG 117--comparing DDI with AZT in patients who have
taken AZT for a year or longer.
The purpose of this study is to see if DDI is better than
AZT for patients who have already taken AZT for a long time, and
may have developed resistant virus.
To enter, volunteers must have AIDS or advanced ARC, as
defined above, and have taken AZT for at least 12 months. They
must at least 12 years old. Again there are many other entry
criteria, so potential volunteers should ask their physicians, or
obtain the full eligibility information thenmselves.
* ACTG 118--test of DDI in patients who cannot tolerate AZT.
For this study patients must be ages 12-99, have AIDS or
advanced ARC, and have shown hematologic intolerance to AZT at
least twice--at least one of those times at doses of 500 mg per
day or less. Intolerance must be documented by specified
decreases and levels of either hemoglobin or neutrophils. AZT
must have been taken for at least 10 weeks but not more than a
year, at doses of 500 mg per day or more. There are various
other entry criteria, much like those of the other two studies.
ACTG 118 will take place at about 50 sites around the United
States. 350 patients will be enrolled.
For more information on any of these studies, call the U. S.
Public Health Service information number, 800/TRIALS-A.
DDI Availability for Persons Who Cannot Enter the Above Tri-
als
Persons who do not meet the criteria for any of the three
trials, or who live too far away from any of the trial sites, may
be able to receive it through one of two other programs. Unfor-
tunately many others will be excluded from these programs by
their restrictive entry criteria--criteria which might be relaxed
in the future.
* "Treatment IND" for people who cannot tolerate AZT.
Patients must be 12 or older, have a diagnosis of AIDS or be
symptomatic, and have a T-helper count of under 200. They must
be intolerant to AZT in any one (or more) of seven ways: decrease
in hemoglobin at a rate of at least 2 grams/month, a decrease in
neutrophils to less than 750, severe nausea or vomiting, intract-
able headaches, acute psychosis, severe agitation, or loss of
muscle strength. Any of these except the hemoglobin must have
happened at least twice (i.e., happened again on rechallenge with
AZT), and patients must have remained intolerant even when the
AZT dose was reduced to 500 mg per day or less.
In addition, patients who are too sick will not be allowed
in this program. At least for now, patients must have hemoglobin
of at least 8.0, platelet count at least 50,000, neutrophils at
least 600, bilirubin, SGOT, and SGPT within 5 times upper limit
of normal, creatinine less than 2.5, alkaline phosphatase within
five times the normal limit, uric acid less than 7.5, and amylase
less than or equal to twice the normal upper limit. These lab
criteria must be met within 14 days prior to initial DDI dosing.
Patients cannot require systemic chemotherapy in the first three
months of DDI treatment, or have acute pancreatitis, a poorly
controlled seizure disorder, or grade B or greater peripheral
neuropathy. Women cannot be pregnant or breast feeding. Patients
cannot concurrently take AZT or phenytoin (Dilantin), and they
will also be excluded if they have taken any antiviral except AZT
within 15 days. Extra tests are required for the first four
months of DDI use if patients are concurrently using any of a
number of drugs, including ganciclovir, acyclovir, ketoconazole,
or sulfa drugs, or if patients have intractable diarrhea or are
following a low sodium diet. Certain other patients considered
at high risk for side effects of DDI must have tests every ten
days while they are using the drug; these patients are those with
"peripheral neuropathy, pancreatitis, seizure disorder, cardiac
abnormalities, gout, and significant elevations of liver function
tests results."
Patients who meet these conditions may receive one of three
different doses of DDI, probably about 375, 250, or 167 mg twice
daily; the exact dose may depend on body weight. Physicians will
have to submit the required data to Bristol- Myers every 30 days
to receive the next 30-day supply of the drug. The DDI will be
free, but patients will apparently be responsible for payment for
the required laboratory tests and medical care.
* Open label use of DDI for patients for whom AZT is not
working.
To qualify, patients must have AIDS (not ARC), have used at
least 500 mg of AZT for at least six months, and be at least 12
years old. Despite AZT, they must have had any one of the fol-
lowing: specified weight loss, marked neurological deteriora-
tion, AIDS-defining opportunistic infections at least three times
in the last six months, T-helper count under 50 on two occasions
at least a month apart, or Karnofsky score 40 or less due to
AIDS. As with the treatment IND above, they cannot take AZT
together with DDI, cannot take Dilantin, and cannot use chemoth-
erapy in the first three months of DDI treatment. There are
other criteria like those of the treatment IND, above.
There are other exclusion criteria not mentioned here. Do
not rely on this outline of some of the rules for access to DDI,
but consult a full and current copy, obtained as described above.
Comment
The program outlined above will clearly exclude many people
who might be helped by DDI, have no other viable treatment
options, and cannot get into any of the clinical trials.
Excluded patients include:
* Children under 12;
* Persons who are too ill to pass the laboratory criteria
required, some of which do not seem to have any relationship to
known risks of DDI;
* Persons who would be on AZT except that they need ganci-
clovir or other incompatible treatment;
* Persons with ARC who are failing on AZT but not intolerant
to it;
(These people might be able to enter a trial where they
could be randomly assigned to receive AZT, known not to be work-
ing for them. Are they being excluded from access in order to
force them into a trial which will make AZT look bad and there-
fore DDI look better in comparison? )
* Persons who cannot afford primary care, cannot afford a
physician willing to fill out the required forms, or cannot
afford the required laboratory tests. This may be the largest
excluded group of all. We urgently need workable procedures to
extend access to DDI (and other "parallel track" experimental
drugs) to patients who use public clinics--perhaps by letting a
panel of physicians in each clinic decide locally who should be
given the drug, without the expensive laboratory tests and paper-
work required by the present system.
According to the September 28 press release from the U. S.
Department of Health and Human Services, the treatment IND and
open label use are "consistent with the parallel track concept
and (is) an interim measure to make a promising investigational
therapy available for people with AIDS who do not have satisfac-
tory treatment options." It is likely that less restrictive
access will be allowed in the future. Under the current rules
there will be many extreme cases of people who clearly should
have access to DDI but are denied it. As a result there will be
much pressure to make access less restrictive.
The basic concept of "parallel track" is that after an
experimental drug has passed initial safety tests and shows some
evidence that it works, persons who cannot get into the formal
efficacy trials should be allowed access to the drug, while the
trials are going on, if they have no other treatment options.
Ultimately, we believe that this concept does not go far enough.
It is wrong to force people into trials by denying them other
treatment options. Instead, trials should be better designed to
take patients' needs into accounts. And if necessary, subjects
should be paid for participation in trials; everyone else
involved in the drug-approval process is paid, as are most
healthy volunteers in medical-research studies.
But politically there is not now enough support in the AIDS
scientific establishment for patient-physician choice and truly
voluntary participation in trials. Instead, the AIDS community
and part of the scientific community have in effect reached a
compromise--that parallel track treatment access should be avail-
able, but only to those who could not enter the formal trials, so
that their access to treatment does not reduce the number of
volunteers and therefore delay completion of the scientific stu-
dies. Many hard-liners in the scientific community do not accept
this compromise, however, and are waiting for the current effort
(to allow limited access to DDI outside of trials) to fail.
Our immediate task concerning access to DDI is to support
the formal trials, and also to push to expand the parallel access
so everyone who needs an antiviral and cannot use AZT will have
the option to use DDI, if the best available information suggests
that this drug is appropriate for them.
Note to Physicians
Physicians who want to make DDI available to their patients
must first register themselves with Bristol-Myers, by calling the
VIDEX Information Center, 800/622-7999, Monday through Friday,
8:00 AM through 8:00 PM Eastern Time. ("VIDEX" (TM) is the
proprietary name for DDI.)
Physicians only should call this number. Anyone can get
information about clinical trials of DDI, or other AIDS drugs, by
calling the Public Health Service hotline at 800/TRIALS-A.
*****
"COMPOUND Q" RESULTS RELEASED
by John S. James
On September 19 Project Inform presented the results to date
of its study of the treatment use of trichosanthin, commonly
known as "compound Q. " This controversial project organized
nine physicians in four cities (San Francisco, New York, Los
Angeles, and Miami/Ft. Lauderdale) to employ a very extensive
and rigorous data-collection protocol to obtain good-quality
information on the results of treatment with trichosanthin.
Patients had obtained the drug from China, where it is used to
induce abortions and to treat certain cancers.
Trichosanthin is not a cure for AIDS, and it can be very
toxic for certain patients. Project Inform has urged that no one
use it without expert medical supervision--and that if, after
careful consideration, anyone does decide to use this treatment,
their physician should first consult with other physicians who
have experience in using the drug and managing its side effects.
But although it is dangerous, this drug is also potentially
very important. AIDS TREATMENT NEWS interviewed Martin Delaney
of Project Inform, who helped to coordinate the study, to learn
more of what is known about this treatment today.
Note: Of the four cities mentioned above, Project Inform
has reported detailed efficacy results from only two, San Fran-
cisco and New York. The Florida arm, which pioneered this treat-
ment program, used a different protocol, different laboratories,
and sometimes a different route of administration; its results
are not entirely comparable, and they have been reported
separately (see below). The Los Angeles results are not complete
at this time. However, Project Inform's report on toxicity and
safety- related information includes what was known from all four
of the centers.
Toxicity of Compound Q
Two kinds of toxicity were found. One appeared to be dose-
related. The other did not seem to depend on the dose, but
rather on the condition of the patient.
The most important toxicity was central nervous system
effects, which were seen in six of the 52 patients reported on by
Project Inform. Three cases were especially serious, involving a
coma, severe dementia, or seizure. Two of these patients have
died, and while the deaths did not appear to result from the
drug, there is controversy over whether or not the drug might
have contributed.
The other four had disorientation or confusion lasting for
hours or days. The longest-lasting case occurred before the
researchers knew about the use of Decadron (dexamethasone) to
control these side effects.
These neurological effects (which often start 30 hours or
more after use of the drug) did not appear to be dose related, as
the doses had varied by three fold (10 to 30 micrograms per kilo-
gram). Instead, the problem appeared to depend on the condition
of the patient. Their T-helper counts were very low, an average
of 23. Four of the seven patients who experienced neurological
effects had had an MRI scan; in three of these four the scan was
suspicious. Every patient who has had a suspicious MRI scan has
had problems.
Mr. Delaney knows of two different theories of what causes
these neurological side effects in some persons with HIV who are
treated with trichosanthin. (In China, where the drug is used
for people without HIV infection, such effects are rare.) :
* One theory is that the drug kills HIV-infected glial cells
in the brain. Glial cells can be replaced. But there may be
problems if too many are killed at once.
* Another theory is that HIV dementia can be caused by a
toxic protein which is released by infected macrophages, without
any brain infection. Suddenly killing these macrophages releases
more of this protein into the bloodstream.
It might be possible to control these side effects by better
testing to tell which patients are at high risk, by treatment
with Decadron or other drugs (perhaps before the symptoms start),
or by beginning trichosanthin treatment with very low doses in
certain patients. But at this time no one is sure that the
danger can be controlled. Persons with very low T-helper cells,
or with any evidence of dementia, seem to be at highest risk.
A different and less serious kind of side effect does seem
to be dose related. Most patients have some degree of muscle
aches, especially of the back and shoulder, relatively minor fev-
ers, joint pains, irritability, and/or rashes. Various drugs are
being used to prevent or relieve these effects.
There are also other dangers. Trichosanthin can cause tem-
porary immune suppression, making existing infections more
severe. Antibodies can develop against the drug, which may limit
future use; test doses must be used to avoid the danger of severe
reactions. Only one such reaction has been seen in the Project
Inform study (in a patient with high T- helper cells), and it was
easily controlled by the immunologist who administered the tri-
chosanthin.
On September 24 Project Inform distributed a warning which
listed the kinds of patients at greatest risk for a bad reaction
to trichosanthin. Those at high risk include:
* Persons near death, as very ill patients have not done
well with this treatment.
* Those with low T-helper counts, less than 100 and espe-
cially less than 50, and with any indication of neurological dam-
age by HIV.
* Those with low T-helper counts and no evidence of neuro-
logical problems are also at some risk.
* Persons currently fighting any active infection (since
trichosanthin causes temporary immune suppression which can make
the infection worse).
* Patients with a history of allergy to other drugs.
* Patients with KS. (Two persons with KS may have had their
lesions worsen.)
Potential Benefits
With these dangers and side effects, trichosanthin might be
discarded if it were only another drug like AZT or DDI. But
unlike other treatments, trichosanthin kills HIV-infected cells,
so it might be able to reduce the total amount of infection,
rather than just slowing its spread. What do we know from the
Project Inform study about potential benefits?
* P24 antigen level--a measure of HIV viral activity--was
greatly reduced, although later it started to rise again. This
test could not be given in New York, because a state law there
prevented physicians from using it. But in San Francisco, of 15
patients who were p24 positive and evaluable, 9 still had a sus-
tained drop two or three months after administration of tricho-
santhin. No other antiviral had been used in this period. The
mean p24 level dropped 66 percent after the treatment, a drop
sustained for at least two months.
Those who had high p24 levels (over 100 by the Coulter
assay) were most likely to improve. Most of these patients had
been on AZT for one to two years when their baseline (pre tricho-
santhin) p24 levels were measured. Then they had been off AZT
during the two to three months before their last p24 measurement.
* T-helper cells improved. In San Francisco, where five of
the patients were healthy and 14 very ill, T-helper cells showed
a 12 percent gain. In New York, where the patients where
healthier over all (mean T-helper count was 129), there was a 42
percent gain. Patients with under 100 T-helper cells did almost
as well (22 percent increase) as those with over 100 (27 per-
cent).
Separate averages were computed for various subsets of
patients. Those who took lower doses (less than 20 micrograms
per kilogram) had a 52 percent T-helper gain, while those with
high doses had a 14 percent gain. The lower dose may have been
more beneficial.
A more detailed breakdown shows that those with high T-
helper cells seemed to do best with a low dose, but those with
low counts to start did best with a higher dose. Those who
started with high T-cells and used a high dose had only a seven
percent gain. But those with high T-cells who used a low dose
had a 188 percent gain. Those with low T-helper counts did
better on the high dose, however, with a 201 percent gain; those
with low T-helper counts who used the low dose had only a 19 per-
cent drop.
One week after the last infusion, T-helper counts were often
down by five to 15 percent, possibly because some of the T- cells
were infected and killed by the drug. This drop was temporary.
* The sedimentation rate (a measure of overall inflammation
or infection) improved 47 percent in the San Francisco group, 15
percent in New York (where the patients were not as seriously
ill).
* There was no important change in liver enzymes or other
blood chemistry. Total white counts went up after treatment, but
in two months they were back to near baseline levels.
* Patients who were AZT resistant appear to be benefitting
from AZT again. They had stopped AZT during the trichosanthin
treatment, but have now started it again. Typically, p24 values
had remained high despite use of AZT. After treatment with tri-
chosanthin, the p24 declined sharply, then started to move back
up. At this time AZT was effective in lowering p24 levels, when
it had not been effective before.
* In the San Francisco group, six of 19 patients had weight
gains over five pounds. Twelve of the 19 reported substantial
improvement in energy, or improved in their Karnofsky performance
rating. In one patients with documented dementia, there was men-
tal clearing; one is now able to work after being unable to do so
for over two years (and spending 16 to 18 hours a day in bed).
One tested negative for cryptococcus for the first time in two
years; besides trichosanthin, his only other treatment was
garlic.
The physicians involved in the study have come to feel that
they need this tool (trichosanthin), in certain circumstances.
But because of its serious dangers, the drug must be used care-
fully. Physicians still need to learn much more about the best
ways to administer this treatment.
A more detailed report of the results of this trichosanthin
treatment protocol is being prepared for publication in a medical
journal.
Florida Study Report
As mentioned above, this treatment program involved physi-
cians and patients in four locations. One of them, Miami/Ft.
Lauderdale, started earlier and used a somewhat different proto-
col, so its efficacy results were not included in the Project
Inform report above. Instead, results have been published in a
27-page document, Trichosanthin Treatment of HIV Induced Immune
Disregulation (final report, September 20, 1989) by Robert A.
Mayer, M. D., Paul A. Sergios, and Kathy Coonan.
This report, describing the treatment of 20 patients, is
hard to summarize. It does reinforce the suggestion of the Pro-
ject Inform report that trichosanthin might be a valuable drug,
but that it also can cause serious side effects which need proper
medical management.
*****
HYPERICIN NOTE
On June 2, AIDS TREATMENT NEWS published a survey asking our
readers to let us know about their experiences with herbal
extracts containing hypericin, an antiretroviral which has proven
effective in animal tests, but not yet been tested in humans. It
has taken longer than expected to analyze this survey and prepare
a complete article for publication. This note will outline what
we have learned so far; we will publish a full report later.
A total of 101 people responded to the survey by the time of
our deadline. (Those who replied after the deadline will also be
counted, but they will be analyzed separately.) Of the 101, 24
reported side effects and 77 did not. 57 reported benefits, 35
did not, and 9 were asymptomatic and did not have blood work
available, so they had no way to tell whether or not they had any
benefit.
Almost all of the side effects were minor, such as loose
bowel movements, minor drowsiness or fatigue, or increased
appetite (unwanted). Only one person reported rising liver
enzymes; most of the respondents apparently had not been tested.
Several people reported increased sun sensitivity, usually minor.
The benefits believed to be due to hypericin were more
dramatic. Of the 57 who reported benefits, 20 named increased
energy; 14 others listed improved well being, feeling better,
etc. Nine had T-helper cell increases, and three had p24 antigen
go negative. (Few respondents had been p24 positive, and few had
test results before and after using hypericin). Several listed
clearing or improvement in chronic opportunistic infections.
It is hard or impossible to get definitive information from
such a survey, because of unknown biases due to self-selection of
those who responded, lack of uniform clinical evaluation or
laboratory testing, and the lack of objective evidence of whether
a benefit or side effect was due to the treatment. Nevertheless
this survey does suggest that hypericin herbal extracts may be
helping at least half of the people who are using them, and that
no serious problems have appeared so far.
*****
PML TREATMENT UPDATE
by Denny Smith
Two Los Angeles activists, Peter L. Brosnan and Lisa A.
Muller, have compiled an exhaustive report on the treatment of
progressive multifocal leukoencephalopathy (PML). AIDS TREATMENT
NEWS mentioned this report in issue #79, and since then Lisa and
Peter have added new information to the list of possible treat-
ments for PML. The report includes all referenced articles from
medical journals, making it useful for AIDS clinics and physi-
cians as well as individuals.
PML is caused by the JC papovavirus, which infects much of
the population but is ordinarily controlled by an intact immune
system. An inflammation of JC results in progressive neurologi-
cal impairment which might resemble that of some other HIV-
related infections: toxoplasmosis, herpes encephalitis, or cryp-
tococcal meningitis. Any these can be life-threatening, so some-
one who is experiencing neurological symptoms like unusual vision
problems, arm or hand uncoordination, difficulties with balance
when walking or standing, confused speech, or disorientation
should be seen by an AIDS- knowledgeable physician immediately.
A diagnosis of PML is very serious, and a completely effec-
tive therapy has not yet been found. Several experimental
approaches are now obtaining some success, so no one facing PML
should be denied an informed attempt at treatment, as has often
happened in the past. The address listed in AIDS TREATMENT NEWS
#79 for ordering the report has changed. Interested people should
now write to: Lisa A. Muller, 3031 Angus St., Los Angeles, CA
90039. For urgent requests, call 213/666-0751. Indicate if only
the recently added information is desired. For both the update
and original report, a donation of $10 (or $15 for overnight
delivery) is appreciated to help pay for copying and mailing.
*****
BUYERS' CLUB IMPORTS LOW-COST AEROSOL PENTAMIDINE
On September 22 the PWA Health Group in New York announced
that it will help people import pentamidine from England, where
it costs about a fifth as much as in the United States.
In the U. S., a 300 mg vial of the drug, enough for one
month's treatment of aerosol pentamidine, costs $99. wholesale.
In England, the same drug sells for $26. retail. There are also
great variations in the prices which U. S. physicians and hospi-
tals charge to administer the drug.
Pneumocystis is still the leading cause of death from AIDS,
despite an effective (and now approved) treatment to prevent it.
A major reason for these preventable deaths is that many people
cannot obtain preventive treatment because of inability to pay.
Much less expensive treatments, such as bactrim or dapsone, are
available, but many patients cannot tolerate them.
The PWA Health Group pentamidine project is endorsed by ACT
UP/New York, Body Positive, Community Health Project (CHP), the
Community Research Initiative (CRI), Gay Men's Health Crisis
(GMHC), Lambda Legal Defense and Education Fund, New York Physi-
cians for Human Rights, People With AIDS Coalition, and Project
Inform.
For more information, call the PWA Health Group at 212/532-
0280. To purchase pentamidine, a prescription is required. The
cost, including customs, shipping, and handling, is $40.
*****
NO ISSUE PUBLISHED SEPTEMBER 22
AIDS TREATMENT NEWS did not publish an issue on September
22; the last issue was #87, published September 8. All subscrip-
tions will be extended one issue to compensate.
*****
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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