
Subject: AIDS Treatment News #226
Date: Jul  7 1995 (891 lines)

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J O H N   J A M E S  writes  on  A I D S
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Copyright 1995 by John S. James;
permission granted for non-commercial use.

AIDS TREATMENT NEWS #226, July 7, 1995
phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:  [items are separated by "*****" for this display]

Combination Antiretroviral Treatment:  New Views, Evolving
   Practices
Combination Treatment and Single Drugs:  Interview with
   Margaret Poscher, M. D.
Protease Inhibitor:  Roche Lottery Deadline July 21
Wasting Syndrome -- Affordable Treatments
Animal Cell Transplantation:  FDA Meeting July 13 and 14
NAC Users:  You Can Help NAC Research


***** Combination Antiretroviral Treatment:  New Views, Evolving
Practices

by John S. James

     The interview with Dr. Margaret Poscher, below, is the first
in a series of articles and interviews on combination anti-HIV
treatment.  For over a year, it has been almost a cliche that
combination treatment is the wave of the future; however, the
actual data on how well drug combinations work in people has
been, and still remains, minimal and disappointing.  But new
information has recently renewed our interest in this potential
advance:

     * Laboratory studies are showing that some combinations work
much better -- or much worse -- than might have been predicted,
in suppressing HIV in laboratory cultures.

     Some of these studies have been conducted over the last five
years by Marty St. Clair, Ph.D., of Burroughs-Wellcome (now Glaxo
Wellcome).  Among the few drugs that she has tested so far, she
has found that certain triple combinations work best.  Some of
the best results have been with AZT, plus either ddI or ddC, plus
either 3TC or nevirapine.

     These laboratory studies have also suggested that it is
better to combine drugs than to alternate them.  Also, it is
usually best to begin the different drugs at or close to the same
time, if possible; the combinations may be less effective if the
patient has already been using one of them for months or years,
allowing resistance to develop.  And the laboratory tests suggest
that these combinations may be most active when the viral
concentration is low, suggesting that they may work better in
early stage HIV infection, than in late stage.

     Conditions in the human body, of course, are very different
than in laboratory cultures.  Therefore this laboratory work can
only provide guidance or suggestions as to what combinations may
be likely to work.  Only human trials can tell whether or not a
particular regimen is truly promising.

     Dr. St. Clair presented a preliminary report on this
laboratory work last January at the 2nd National Conference on
Human Retroviruses and Related Infections, in Washington, D. C. A
full report will be published soon.

     * Recently we heard about a case of very successful use of
one of the combinations suggested by the laboratory work (AZT
plus 3TC plus ddC), by a person we know.  His CD4 (T-helper)
count was 300 a year ago, then declined rapidly to 110 last
November 1, and to 70 last December 1, when he started the triple
combination treatment.  In February his count was 320, and in
March it was 540.  In April he had a bad case of flu, and his
count dropped to 420.  Then it went up to 450, and in June 1995
was 480.

     In November he had hairy leukoplakia, bad thrush, and bad
scalp lesions; he had lost weight and was sleeping up to 18 to 20
hours a day.  Now all symptoms are gone, and he has gained 25
pounds and is sleeping normally.  He appears to be in perfect
health.

     This person, importantly, was treatment naive when he
started the triple combination.  He used standard doses of the
drugs, but sometimes reduced the AZT dose from 500 mg to 400 or
300, due to stomach upset.  He was using no other treatment at
the time except for acyclovir.

     Certainly no single case can prove that a treatment works;
and we suspect that few people will find equally good results
from this combination.  But still cases like this compel
attention, since comparable results are never seen with
conventional HIV treatment.  We mentioned this experience because
it suggests a possibility, a goal, worth aiming for. Also, it
suggests designs for clinical trials; for example, if a patient
has a CD4 count below 50 and has CMV retinitis, and combination
HIV therapy raises the CD4 count to a level where CMV is not
normally a risk, will the retinitis stop progressing, thus
reducing or eliminating the need for specific CMV treatment?

     * On June 30, Glaxo Wellcome applied to the FDA for
accelerated approval for 3TC, for use in combination with AZT as
first-line treatment for adults with CD4 counts under 500, and
for children who meet the CDC guidelines for treatment with
antiretrovirals.  If the drug is approved for this indication, it
will probably make combination treatment the standard of care for
many (though not all) persons under 500, making it much easier to
get this treatment paid for.  It will also encourage
experimentation with three-drug combinations, as approved drugs
like ddI or ddC are added to the regimen.

     Today, combination antiretroviral treatment, especially
triple combinations, are more talked about than used.  As we
asked around for referrals to physicians who might have
experience with triple combinations, the same names kept coming
up again and again.  Most of them have only used triple
combinations with a few patients.  And they have different
approaches to when and how they use these treatments; consensus
has not yet developed.  This slow start for combination treatment
is not surprising, due to the lack of definitive data from
clinical trials.

     The interviews in this series will examine some of the
different approaches which are in use, and why physicians make
the choices they do.  Note that these interviews will focus
primarily but not only on combination treatment; they will also
look at related medical topics when they arise.


***** Combination Treatment and Single Drugs:  Interview with
Margaret Poscher, M. D.

by John S. James

     Margaret Poscher, M. D., is an internist in private practice
with Quest, a five-physician medical group in San Francisco. Dr.
Poscher is also Assistant Clinical Professor, University of
California Medical Center, and Director of HIV Clinical Services,
University of California Mt. Zion.

     ATN:  Which antiretroviral combinations do you most use or
prefer?

     Dr. Poscher:  I am disappointed that there is still not much
published information on combination therapy.  I was on the fence
about combinations for a number of years.  But in the last two
years, and especially with viral load assays now available, it
has become clear that combination treatment is incredibly
important.  I don't think I have any patients on monotherapy,
except for some on d4T.

     My favorite combination now is AZT plus 3TC. I foresee that
as being initial therapy, when 3TC is approved; patients who have
CD4 (T-helper cell) counts below 500, or have a certain threshold
level of HIV RNA, will be started immediately on this
combination.

     At this point, with patients who are asymptomatic and have a
relatively high CD4 count, and a moderate viral load, between
10,000 and 100,000 copies of RNA, I am starting those patients on
AZT plus ddI, or AZT plus ddC.  They make the decision of ddC or
ddI, based on my description of the two drugs.  I tend to prefer
ddI, as I have not been impressed with ddC as an antiviral.

     This week I had a patient who recently seroconverted, and in
a big way -- with several million copies of HIV RNA, a big dip in
his CD4 count, and who continues to have over 100,000 copies of
RNA.  In 1995 there is concern about people becoming infected with
AZT-resistant virus.  So we discussed potentially starting him on
d4T as initial therapy, and using d4T with either ddI or 3TC.  I
think that d4T with ddI is a very good combination, especially in
people with higher T-cells, who tend not to get neuropathy as
easily as advanced patients.

     In patients I've had on AZT plus 3TC who have developed
complications -- especially anemia, the big complication I have
seen, especially in patients with more advanced disease -- I've
had success switching them to d4T plus 3TC.

     Occasionally I will use the triple combination AZT plus 3TC
plus ddI; this is based on Dr. St. Clair's report at the 2nd
National Conference on Human Retroviruses and Related Infections
(January 29 -- February 2, 1995, in Washington, D. C.)  on
laboratory studies with this combination.  Since then there has
been a question raised about possible antagonism between ddI and
3TC, but this is not yet substantiated.  With these untested
combinations, we do have to be careful about unknown potential
antagonisms.

     ATN:  Any other thoughts about which patients are the best
candidates for which treatments?

     Dr. Poscher:  It is probably also important to look at the
viral load.  People with very high levels of HIV RNA, I would be
more likely to put on a triple combination.  Some patients may
want to start therapy very early; they may only have 15 or 20
thousand copies of RNA, and CD4 counts of 500 or above; you might
even consider monotherapy for somebody like that.  Or I might put
them on AZT plus ddC, as ddC is easier to take that ddI.  With
high viral loads, I would dose higher, and give more drugs, at
least initially, until the viral load drops.

     ATN:  On doses, do you tend toward the lower end of the
standard range?

     Dr. Poscher:  I tend to give low doses.  For AZT, I give 300
or 400 mg per day total.  With ddC, I refuse to use the 0.75 mg
tablet; my experiences with ddC back when it was in parallel
track was that higher doses just meant more neuropathy and more
anemia when used with AZT.  So I tend to stick to 0.375 mg of ddC
three times a day.

     With ddI I also use low doses, because of problems with
pancreatitis which I saw when the drug was parallel track; my
cohort of patients had close to a 20 percent incidence of
pancreatitis.  But that is when we were using total daily doses
of 750 to 900 mg.  Now I tend to give 250 mg of ddI once per day.
I was sad to see the 375 mg sachet taken away, because I had many
patients on 375 mg once per day.  I dose it once a day for
convenience for the patient; most patients cannot find two times
in a day when they have an empty stomach, since usually they are
trying to eat as much as they can to maintain their weight.  To
try to fast for an hour to be able to take ddI twice a day
usually means missing a meal, at one end of the day or other.  So
I encourage them to take it in the middle of the night, if they
wake up to urinate, as they often do.  If you make it easy for
people, they are more likely to take the drug; it is better for
them to get one good dose in than skip it altogether because it's
inconvenient.

     ATN:  What differences do you see with therapy naive
patients, vs. those who have been on AZT for a long time?

     Dr. Poscher:  It's like night and day; it is significantly
different.  I think 3TC is the one exception, where you can add
it to AZT and still get some mileage out of the AZT.  I have
completely given up on adding either ddI or ddC to a patient who
is already on AZT; I think that is a waste of time.  When you
start a naive patient on antiretroviral treatment early on, that
is where those two drugs have a role -- but not in somebody who
has been on AZT for three or four years.  The only drugs I could
see adding then would be 3TC, or potentially a protease inhibitor
if that were available.

     For patients who are on AZT and not eligible for 3TC today
because they have a CD4 count over 100, I usually switch them to
d4T, usually to a combination of d4T and ddI.

     ATN:  Do you switch them all at once to the combination, or
do you start one drug first?

     Dr. Poscher:  All at once.  Some patients are hesitant; they
want to try one drug and start at a low dose and get used to it.
But I encourage people to go for it, take both drugs full dose
from day one.

Acyclovir

     ATN:  What about other antivirals, such as acyclovir, or
oral ganciclovir prophylaxis?

     Dr. Poscher:  I'm pro acyclovir -- absolutely for people who
have a known history of herpes, or zoster.  I have all of them on
suppressive doses of acyclovir, 400 mg twice daily.  A few
patients don't want to take it; they are usually patients who
have never had herpes or zoster outbreaks.  Still I encourage
them to consider it, as I think there are other herpes viruses
which are not clinically apparent which are exerting some effect.
And acyclovir is safe; there is no major drawback to using it.
In the six years I have been in private practice, I have seen two
cases of acyclovir-resistant herpes, after treating many people
with acyclovir.

Oral Ganciclovir

     Oral ganciclovir for CMV prophylaxis, I am still ambivalent
about.  I am concerned about the potential for resistance; I
think it is far more likely with ganciclovir and CMV, than with
acyclovir and herpes.  I have had a couple patients who have been
on protocols for oral ganciclovir prophylaxis and have then
developed CMV, and it has been a nightmare.  One patient was
resistant to everything; oral ganciclovir led to ganciclovir
resistance, and before he saw foscarnet he was foscarnet
resistant, and he was also resistant to HPMPC.

     My thinking now is that there are better therapies coming
for CMV, such as local therapies through injection or eye
implants.  With these we have a better chance of conserving
retina, which I think is the important thing, than through years
of treatment with oral ganciclovir and its complications.  So I
am leaning to not using oral ganciclovir in patients who have no
CMV whatsoever, and to be careful with ophthalmologic followup --
frequent eye exams, and alerting people to symptoms of CMV
retinitis.

     I would use oral ganciclovir in patients who had end-organ
CMV disease -- CMV esophagitis, colitis, gastritis -- but have
not yet developed retinitis.  Here you might use oral therapy as
secondary prophylaxis essentially -- as those patients will
probably develop retinitis within six to 12 months.

     For treatment of CMV retinitis, people often do well with
oral ganciclovir, after an initial course of IV induction
treatment.  I have had a couple patients recently who have gone
one year without a recurrence, on oral ganciclovir.

Other, Miscellaneous

Potential HIV Treatments

     ATN:  Are there other therapies that many of your patients
are on, such as experimental immune modulators?

     Dr. Poscher:  I have probably a dozen who continue to use
DNCB. Many continue to be on the TP-5 protocol.  A few are
interested in the Cytolin, a mouse monoclonal antibody; I have
not seen enough on that to form an opinion.  I think the
enthusiasm for IL-2 has diminished; nobody has asked about it in
months.

     Thalidomide is the newest.  I used it several times over the
past several years, in patients with oral aphthous ulcers, and
found it to be a very easy drug to take.  The patients I had who
were maintained on thalidomide seemed to do very well; I used to
wonder if maybe the thalidomide was doing something for them [vs.
HIV disease, not only vs. the ulcers].  So I'm encouraged that we
at least have access to it now, as a potential treatment for
wasting, and possibly for MAC, since it has been used in the
treatment of leprosy for decades now.  [See "Thalidomide and HIV:
Several Possible Uses," by Denny Smith, AIDS TREATMENT NEWS #221,
April 21, 1995.]

     ATN:  What kinds of changes are you seeing in CD4 and viral
load with the different combination therapies?

     Dr. Poscher:  One therapy naive patient had avoided starting
antiretroviral therapy for years, and his CD4 count kept going
down.  Finally I insisted that he do the HIV RNA test. His count
was greater than 1,600,000.  He decided to go into a clinical
trial of PMEA; when he finally started that treatment, his viral
load was still over a million, and his CD4 count had dropped
below 200.  He was a perfect example of an antiretroviral naive
patient who was put on the mid dose of PMEA, and his viral load
went from over a million to 30,000, and his CD4 count went from
less than 200 to over 500, after six weeks on PMEA. He is now on
AZT plus 3TC, and doing very well.

     I have seen at least one log (ten fold) viral load
reductions with d4T and 3TC.  And when the RNA goes down, the CD4
count goes up.  Usually it does not last -- but I find that
people often reach a new plateau.  They get a big increase, and
then it comes down a little, and they stay at that new plateau, a
little higher than they originally were, for a good six months,
or longer in some cases.  I've seen people go from well over
100,000 copies of HIV RNA, to under 10,000 copies.

     [Part II of this interview will look at possible side
effects of combination treatment, treating a sudden CD4 drop, and
reimbursement and managed-care issues.]


***** Protease Inhibitor:  Roche Lottery Deadline July 21

     In a widely distributed June 21 press release, Hoffmann-La
Roche announced details of "The Invirase* International
Compassionate Treatment Program."  This program will distribute
saquinavir (brand name, Invirase), a protease inhibitor, to
persons with a CD4 (T-helper) count under 300 who no longer
benefit from approved antiretroviral drugs (AZT, ddI, ddC, and
d4T), and meet other entry criteria.  Roche not only allows, but
even encourages, combination use of its protease inhibitor
together with the approved antiretrovirals.  60 percent of the
slots will be reserved for persons with a T-helper count under
50.  [Note:  Roche uses the spelling "proteinase," instead of
"protease."  The meaning is the same.]

     The drug will be made available to 2,280 patients in the
U.S., 96 in Canada, and about 1700 in Europe and Australia; Roche
has set up a lottery in case more people apply for the drug.  To
get into the first U.S. lottery drawing, your physician must
enter you on or before July 21, 1995.  (When more drug is
available, another lottery will be conducted, including those not
selected from the first lottery, and others who apply later.
Therefore, if you miss this deadline, you can still apply for a
possible subsequent lottery.)

     To get details about this program, you or your physician can
call 800/332-2144, Monday through Friday between 9:00 a.m. and
8:00 p.m. Eastern time.  You can also request information by fax,
800/332-7644; or by mail, by sending a written request for
information to the Roche Data Coordinating Center, P. O. Box
81312, Wellesley Hills, MA 02181.  [In Canada, the program is
slightly different; call 800/257-3741 for Canadian information.]

Comment

     We have not been greatly impressed by the previous data we
have seen on saquinavir, at the doses which will be used in this
program.  The drug seems to be safe, and to be effective; but the
average size of the effect is not that great, unless larger doses
are used.  However, some individuals do seem to benefit much
better than the average.  And new data from Roche (see below) may
make saquinavir a better drug, by showing doctors how to use it
more effectively.  It is too early to judge this drug.

     There have been concerns that people who use saquinavir
alone are likely to develop resistance to it, which may cause
cross-resistance to other protease inhibitors.  If this happens,
it could mean that people who use an early protease inhibitor
might lose the ability to benefit not only from that drug, but
also from better protease inhibitors which may be available in
the future.  This issue has been controversial among experts; for
example, Roche's experts and Merck's experts have disagreed about
it.  Now Roche claims that new data, to be released July 10 at
the Fourth HIV Drug Resistance Workshop in Sardinia, Italy --
data on almost 100 people, compared to the four to six people
that Merck tested -- indicates that saquinavir does not cause 
resistance to other protease inhibitors -- and that the 
development of resistance to saquinavir itself can be reduced by 
using that drug in combination with AZT.  Over the next few weeks, 
we will see how this new information is evaluated by the medical 
community, and by scientists independent of both companies.

     It is also important to realize that different people have
very different individual responses to AIDS treatments.  For some
people, this drug works much better than it does on the average.
One argument in favor of trying saquinavir is to see if it works
exceptionally well for you.

     What if you cannot decide whether or not to apply for the
lottery program, and cannot get an appointment with your doctor
before the deadline?  One strategy is to call and ask your doctor
to apply anyway -- it is easy for the doctor to do, requiring
only a simple form and a copy of a T-cell test from your medical
records.  Everything can be handled by fax. Also, you can start
the whole process on your own, by calling the phone number above
to get information about the program, and advice on getting your
doctor to enter you.

     Later, if you are accepted, there will still be some time
before you actually get the saquinavir; and you can use this time
to meet with your doctor decide whether or not you want to use
the drug.

     We will be surprised if Roche gets 2280 U.S. applicants for
this lottery by July 21.  There just isn't enough time for the
word to get around, for over 2,000 people to hear about the
program, grasp the information, see if they qualify, decide if
they want the drug at all, make doctors appointments, talk with
their physicians, and get the forms turned around, all between
the first detailed press release on June 21, and the lottery
cutoff on July 21.

     On July 5 Roche told us that they were optimistic on filling
the program, as they had 5,000 phone calls after articles were
published in The Wall Street Journal and other newspapers; and
they had several hundred completed applications as of July 3.
Even so, we still doubt that they will get 2280 qualified
applications by July 21.  If they do not, this means that no
lottery will be needed, since all qualified applicants who apply
by that deadline will get into the program.  And there may also
be extra slots for people who apply after July 21; however, we
are not sure about this.

     But on the negative side, failure to fill the lottery in one
month might be wrongly interpreted as lack of public interest in
expanded access, protease inhibitors, or new AIDS treatments,
when in fact the obvious obstacles listed above would be
responsible.  We believe that the expected inability to fill all
slots immediately could have been predicted even before the
program was announced.  Even under the best circumstances it is
hard to inform the public and get people to change their
behavior.  This program has to get over 2,000 specially qualified
patients and doctors to change their behavior together, to follow
a new procedure to get an experimental drug that even the doctors
do not know much about, all within one month after receiving a
form letter or reading an article in a newspaper.

     [Note:  There is also a completely separate program for
access to the Merck protease inhibitor best known as MK-639 (it
has now been given the chemical name indinavir sulfate, and the
brand name Crixivan*); many third-party observers consider this a
more promising drug than low-dose saquinavir.  The Merck program,
which will begin in August or September, will provide MK-639 to
1400 people who have a CD4 count below 50 and meet other entry
criteria.  Information about this program will be announced by
Merck, probably in July.]


***** Wasting Syndrome -- Affordable Treatments

by John S. James

     The May issue of Treatment Issues, published by GMHC (the
Gay Men's Health Crisis, in New York), includes several excellent
articles on treatment of wasting syndrome -- severe loss of lean
body mass not due to obvious causes such as nutritional
deficiency or intestinal infection -- in AIDS.  The bottom line
is that there are inexpensive potential treatments, and some
early experience suggests that most patients can be successfully
treated by using one or another of them.  This may mean that only
a few patients will need the extremely expensive treatments,
which are out of reach economically for most people -- human
growth hormone, which costs about $1000 per week, or total
parenteral nutrition (TPN), which usually costs even more.

     [Note:  While human growth hormone costs about $1000 per
week, the growth hormone for cows (which will not work in humans)
costs $3 per week.  Both are made by similar recombinant
technology; we have been told that the amino acid sequences are
two-thirds identical.  But for people the commercial price is $42
per milligram (somewhat less for "cost recovery" for a special
AIDS program, where the drug has not been fully approved).  For
the closely related agricultural product, however, the price to
dairy farmers, we have heard, is less than 2 cents per milligram.
Someone should investigate how the price of human growth hormone
has remained so disproportionate to the cost of production for
many years.  A number of companies sell this drug throughout the
world -- at the identical price of $42 per mg.  The substance
itself is produced by the body and cannot be effectively
patented; processes for manufacturing it are patented, and there
has been considerable patent litigation.]

     [Persons who need human growth hormone and cannot pay for it
should realize that there is an indigent program, sponsored by
Serono Laboratories, Inc., the company which researched the use
of human growth hormone for AIDS-related wasting. Serono provides
the hormone without charge to a small number of patients who need
it and have no way to pay.]

     An example of an affordable treatment for AIDS-related
weight loss (when not too severe) is testosterone enanthate, used
with an appropriate exercise program.  In some cases nandrolone,
an anabolic steroid, is added as part of the regimen.  While this
treatment has not been proven in clinical trials, some leading
AIDS physicians are using it and finding good results; Treatment
Issues mentioned Marcus Conant in San Francisco.

     "We are frequently using testosterone to treat people with
AIDS-related weight loss," Dr. Conant told AIDS TREATMENT NEWS.
"And in some cases we are also using nandrolone when these people
have shown some promise of weight gain."  Dr. Conant explained
that the nandrolone generally worked well only in those who had
already responded successfully to the testosterone.

     What about people with true wasting -- who have lost more
than ten percent of their body weight, and continue to lose
weight despite testosterone, exercise, and nandrolone?  Dr.
Conant's team has found that these people respond very well to
human growth hormone; 14 of the 16 severely wasting patients they
have treated have gained weight with the hormone, according to
Gordon Sanford, PA-C, a physician's assistant in Dr. Conant's
office.  And they have not found any other treatment which worked
for those patients -- the FDA-approved wasting treatments Megace
or Marinol did not work.  [However, Conant's experience cannot
rule out thalidomide, or ketotifen (see below).  Thalidomide has
seemed to work for severe AIDS-related wasting in small studies;
larger trials are needed to confirm this finding.  Ketotifen has
led to striking weight gain in a few cases; it needs a formal
study.]

     Your physician can call Dr. Conant's office in San
Francisco, and talk to Dr. Conant, or to Gordon Sanford, to learn
the doses, and other critical details and important information
on how to use testosterone treatment most effectively.

     [Note that this discussion of testosterone, and the other
potential wasting treatments below, assumes that the patient has
already had a complete workup to look for any obvious causes of
weight loss, such as parasites or other intestinal disease, MAC
or certain other infections, lymphoma, inadequate food intake,
etc. These specific causes need to be considered first.  The
potential weight loss/wasting treatments mentioned here are tried
when such specific causes cannot be found.]

     Another affordable possibility for treating wasting syndrome
is ketotifen, believed to be a very safe drug, which is widely
used in Europe for asthma and allergies, but not approved in the
U.S.  You can get ketotifen through the PWA Health Group in New
York (phone 212/255-0520).  The main drawback is that not much
research has been done yet on using it for AIDS-related wasting;
also, since the drug is not regularly used in the U.S., most
doctors here will not know anything about it.  The main advantage
is that there seems to be little risk, cost, or other "down side"
to trying it.

     A third affordable possibility is thalidomide, which is now
available under a special, tightly controlled "underground
compassionate access" program through the PWA Health Group, or
through Healing Alternatives, a similar buyers' club in San
Francisco.  (Thalidomide is also available through an official,
FDA-approved compassionate access program for people with AIDS,
but at this date that is only for treatment of aphthous ulcers,
not for treatment of wasting.)  The main danger, of course, is
birth defects if this drug is taken in pregnancy.  In addition,
larger doses of thalidomide can cause neuropathy or other adverse
effects.

     Two treatment are FDA-approved for AIDS-related wasting
syndrome:  megestrol acetate (Megace), and also dronabinol
(Marinol), which uses the active ingredient of marijuana as an
appetite stimulant.  Both of these are expensive; and it is
controversial how effective they are for increasing lean body
mass, which is what a wasting-syndrome treatment must do.  The
May Treatment Issues mentions these treatments, but does not
discuss them in depth.  (We have been told by others that persons
who use Megace should have their testosterone levels monitored.)

     [Note:  on July 4 we talked to Dave Gilden, editor of
Treatment Issues and author of an article on human growth hormone
in the May 1995 issue.  He said that if he were publishing that
issue today, it would have more information on exercise, and more
coverage of Megace and Marinol.  Also, he would urge activists to
campaign to get the FDA-approved compassionate access program for
thalidomide expanded to allow persons with wasting syndrome --
not only those with aphthous ulcers, as is the case today -- to
receive the drug.  And he would emphasize the great need for more
research in AIDS-related wasting.]

     We strongly recommend that anyone interested in wasting
syndrome get the May 1995 Treatment Issues; it includes
background and details which we only summarized above.  Better
yet, anyone interested in AIDS treatment can get a complete set
of the back issues of this very useful publication for a
suggested donation of $25.  To order, send $3 for the May issue
only, or $25 for a reprint of all the back issues, to: GMHC,
Treatment Education, 129 West 20th St., New York, NY 10011.  We
also recommend subscribing to Treatment Issues, suggested
donation $35/year (11 issues) for individuals, $70/year for
physicians, institutions, or international subscriptions.

     [Note:  For additional information on wasting and its
treatments, also see "Turning the Corner on Wasting?  A Symposium
on Wasting Disorders," by Jeff Getty, in BETA (Bulletin of
Experimental Treatments for AIDS), June 1995; BETA is published
by the San Francisco AIDS Foundation.  And see Notes from the
Underground, April/May 1995, available without charge from the
PWA Health Group, 212/255-0520.]


***** Animal Cell Transplantation:  FDA Meeting July 13 and 14

by John S. James

     Advances in organ and cell transplantation, and in basic
immunology, have now raised the possibility of transplantation of
organs or cells from animals to humans.  For example, it is known
that immune cells in baboons are resistant to HIV infection.  If
these cells could survive transplantation to humans, and could
work properly in humans, they might conceivably provide
immunological resistance to HIV, like human cells do -- except
that the baboon cells could not be destroyed by the virus.  If it
works -- still a big if -- such a procedure might allow the
reconstitution of an immune system in persons with late-stage
AIDS.

     The reverse -- transplantation of human immune cells to a
baboon -- has already been done.  So far the cells have survived,
and tests indicate that proliferation responses are functional,
according to treatment activists who have followed this work
closely.

     The first test of baboon to human cell transplantation was
scheduled to have been tried already; the principal investigators
are transplantation specialists at the School of Medicine of the
University of Pittsburgh, and AIDS specialists at the University
of California San Francisco Medical Center.  Under the Federal
regulations which were in effect until recently, such a test only
needed to be approved by a local IRB (institutional review
board).  It did not need additional approval by the FDA -- just
like a surgeon does not need FDA approval to try a new,
experimental operation. But shortly before the first baboon to
human transplant was to be done, the FDA expanded its authority
into this new area, and told the researchers that they would have
to get FDA approval first.

     The researchers complied, postponing the trial and applying
for FDA approval.  However, animal to human transplantation
involves major issues which must be considered -- including the
theoretical risk of transmitting an animal disease to humans,
conceivably even causing an epidemic.  But this risk must be seen
in perspective.  Animal to human transplants have been attempted
several times in the last 25 years, with some long-term
engraftment; so far no dangerous animal diseases have been
transmitted.  And tens of thousands of people die every year
because of lack of human organs to transplant.

     Some experts believe that there should be more animal trials
first, before attempts to transplant animal tissues into humans.
But others fear that such trials will take years to finance,
organize, and conduct, and cannot be definitive anyway.  Sorting
out all these heavy policy issues might take a long time,
seriously delaying an early proof-of-concept trial.

     The requirement for advance FDA approval could well mean, in
practice, that the very difficult general policy issues for the
whole field of "xenogeneic" (animal to human) organ and cell
transplantation will have to be considered first -- before even
the earliest proof-of-concept human trials can go forward.  A
bureaucracy usually prefers to delay making decisions in a
completely new area, until it has a policy in place.  If that
happens in this case, it could disastrously delay the research.
The alternative is to allow the small, early research to begin,
even while the overall policy is being worked out.

     These matters will be considered at a critical FDA meeting
on July 13 and 14, at the Holiday Inn in Bethesda, Maryland. 
This meeting is open to the public.

     David Hook, of the Xenogeneic Committee of ACT UP/Golden
Gate in San Francisco, told AIDS TREATMENT NEWS that people
should call the FDA's Office of AIDS and Special Health Issues,
301/443-0104, to tell the FDA that the baboon transplantation
trial should go forward without delay.

     For more information, including on how you can be involved,
leave a message for David Hook on the voicemail of ACT UP/Golden
Gate, 415/252-9200.

Comment

     Until now most of the AIDS community has known little about
this issue, which has been brewing quietly behind the scenes for
about two years.  Those involved preferred not to seek publicity
until recently, when the research was threatened with long
delays.

     But now the activists and researchers who want to move this
research forward do need public support.  This situation presents
a challenge to the AIDS community.  We must get up to speed
quickly in this complex and difficult area; otherwise, decisions
seriously harmful to people with AIDS are likely not only to be
made, but also to become institutionalized.

     [Note:  This preliminary article is based on interviews with
treatment activists, and on published information.  Due to time
constraints, we did not interview the researchers.]


***** NAC Users:  You Can Help NAC Research

     If you have used NAC (N-acetylcysteine) for at least three
months, you could help a scientific study at Stanford University
by completing the survey below.  This survey is to tell the
researchers why you are using the treatment -- and what effects
you have seen, good or bad.

     NAC has long been one of the most popular treatments sold in
buyers' clubs; it is also sold in health-food stores.  The
Stanford study, which started over a year ago, has given NAC or
placebo to about 60 volunteers (mostly recruited in San
Francisco), in a double-blind trial (meaning that neither the
volunteers, nor their doctors, nor the researchers themselves,
know who is getting the real drug and who is getting the
placebo).

     Now the researchers are about to break the blind (learn who
got the real drug) and analyze the study statistically.  But
first, they must formulate all the questions they want to ask of
the data; for scientific reasons, it is important that they do
this before they break the blind.  The survey below is to give
them ideas of any questions they should be asking, but may have
overlooked; this survey by itself is not intended to be
scientific or statistically valid by itself, but to help
formulate questions for the analysis of the clinical trial, to
make the trial itself as useful as possible.

     The researchers are especially interested in any changes in
energy, in sexuality, or in neurological symptoms -- or any other
observations which they may have not thought about, but which
might have changed when you started the treatment.

     We encourage you to copy this article so that friends who
have taken NAC can also participate.

The Survey

     For persons who have taken NAC for a total of three months
or longer, please answer the following questions on a separate
sheet of paper, and send your reply to the address below. Please
answer each question separately, using the question number so
that the researchers know for sure which response is to which
question.

     (1) Approximately how long have you taken NAC?  (If you have
discontinued, or stopped and started again, let us know.)

     (2) What is your usual single dose?  How many times a day do
you take this dose?

     (3) What brand of NAC do you use?

     (4) What benefits do you think you may have had from NAC?
Please classify each possible benefit as "pretty sure" if you are
pretty sure it is due to NAC, or "probably" if you think that it
is probably due to NAC.

     (5) Have you had any serious side effects which may be due
to NAC?

     You can also answer the following questions if you wish:

     (6) How long have you known you were HIV positive?

     (7) What were your last CD4 (T-helper) and CD8 counts when
you started taking NAC?  Also, what were your most recent CD4 and
CD8 counts?  And how long ago were they measured?

     (8) Have you had AIDS-defining opportunistic infections?  If
so, which ones, and when were they diagnosed?

     (9) If you are no longer taking NAC, why did you discontinue
it?  Also, have you had any AIDS-defining opportunistic
infections since you stopped taking NAC?  If so, when?

     (10) Please add any additional comments you wish to make.

     (11) Optional:  If you would be willing to answer any
further questions the researchers may have, or if you wish to
receive a summary of the survey responses, include your name and
address.  (On the other hand, you may reply anonymously if you
wish.)

     Please send your answers to:  Stanford NAC Project, c/o
Davies Medical Center, Castro and Duboce Streets, San Francisco,
CA 94114.



***** AIDS TREATMENT NEWS
Published twice monthly

Subscription and Editorial Office:
P. O. Box 411256
San Francisco, CA 94141
800/TREAT-1-2  toll-free U.S. and Canada
415/255-0588 regular office number
fax:  415/255-4659
Internet:  aidsnews@aidsnews.org
Editor and Publisher:
John S. James
Reader Services and Business:
Richard Copeland
Thom Fontaine
Tadd Tobias
Denny Smith

Statement of Purpose:
AIDS TREATMENT NEWS reports on experimental and
standard treatments, especially those available now.  We
interview physicians, scientists, other health
professionals, and persons with AIDS or HIV; we also
collect information from meetings and conferences,
medical journals, and computer databases.  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.

Subscription Information:  Call 800/TREAT-1-2
Businesses, Institutions, Professionals:  $230/year.
Nonprofit organizations:  $115/year.
Individuals:  $100/year, or $60 for six months.
Special discount for persons with financial difficulties:
$45/year, or $24 for six months.  If you cannot afford
a subscription, please write or call.
Outside North, Central, or South America, add air mail
postage:  $20/year, $10 for six months.
Back issues available.
Fax subscriptions, bulk rates, and multiple subscriptions
are available; contact our office for details.
Please send U.S. funds:  personal check or bank draft,
international postal money order, or travelers checks.
VISA, Mastercard, and purchase orders also accepted.

ISSN # 1052-4207

Copyright 1995 by John S. James.  Permission granted for
noncommercial reproduction, provided that our address
and phone number are included if more than short
quotations are used.

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