Subject: PI Perspective #7 (complete)
Date: Nov 1989 (2187 lines)

PI Perspective
Number 7 November, 1989

Project Inform
San Francisco, California

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

Q -- The Real Story
Informed Consent
Q-Induced Mental Status Change
AZT News:  The Final Chapter?
The Road to Parallel Track
Using the PI Hotline
Evaluating Clinical Trials
DDI Fact Sheet
Organizational Update

*****

Compound Q - The Real Story

Amidst a storm of controversy, organizational bickering, and
legitimate scientific interest rivaling the concurrent San
Francisco earthquake, Project Inform this month released
preliminary data from its community-based treatment protocol
using trichosanthin (Compound Q).  The findings of the multi-
center program give a mixed but intriguing picture of a drug
which may offer a new kind of hope, along with serious side
effects which may prevent its use at some stages of illness.
Readers are invited to move directly to the section of the story
of greatest personal interest:  In the Beginning (background on
trichosanthin and why and how Project Inform established the
protocol); Outcomes (findings regarding safety and efficacy); or
The Aftermath (implications for personal use and where to go from
here).

In the Beginning

Compound Q had come to our attention in 1988. The AIDS networks
learned that scientists at the University of California and in
private industry (Genelabs) had filed a patent on new drug which
appeared to selectively kill HIV infected cells.  The discovery
came about through the work of Dr. Michael McGrath, who had been
pursuing new observations about the pathology of HIV, namely that
direct infection of T- cells alone could not account for the
destructiveness of the disease.  McGrath found that in addition
to T4 cells, HIV was infecting macrophages, a common type of
immune system cell found in the blood and many body organs.
Unlike T4 cells, macrophages did not quickly die once infected,
but lived for as long as a year and a half, always able to
produce new virus. They appeared to be the missing reservoirs of
HIV infection which kept the infection alive and well, despite
the rapid death of infected T-cells.  The infection of
macrophages helped explain the disease, perhaps accounting for
all but its auto- immune aspects.

McGrath and company reasoned that HIV infection could be greatly
moderated if the infected macrophages could be destroyed and
replaced with healthy ones, which in turn could be protected from
infection with conventional drugs like AZT. Without doing
something about the infected cells, however, the fight against
HIV was but a futile effort to slowdown the spread of virus to
new cells, while doing nothing about the existing infection.

Chinese researchers brought trichosanthin to McGrath in late
1986.  In his lab, one of a very few in world capable of studying
infected macrophages, it appeared to be a very powerful antiviral
against all forms of HIV expression, and at doses that appeared
safe for human use.  Using fresh human blood from AIDS patients,
the drug appeared to selectively kill infected macrophages and
infected T-cells, while doing little damage to healthy cells.  In
these in in vitro tests, it was more potent and more selective
than any Q other known anti-HIV drug, and it achieved its goals
in an entirely different way.

In China, the drug had been used successfully for more than 20
years for certain cancers and to induce abortion.  It had a good
safety record when manufactured and used properly.

Word of McGrath's findings slowly leaked out in 1987 and 1988,
despite an official blackout while lab research continued, FDA
forms were filed, and patent rights sought.  Despite the
blackout, some individuals learned of the Chinese version of drug
and succeeded in importing it as early as November of 1988.  By
January of 1989, several groups had found sources and some were
beginning to experiment with It.  In February, PI became aware of
a pioneering effort in Florida to evaluate the safety and
effectiveness of Chinese trichosanthin, as well as to treat
significant numbers of patients.  Compound Q suddenly had all the
makings of becoming the next big "drug of the year."

While this sounded good to people interested in trying Q,it also
raised serious concerns.  True, Q might represent a new and more
effective approach to therapy, one which would add to the
benefits produced by any other approach.  Some highly placed
individuals had dared to use the "C" (cure) word in discussing it
in the media.  Yet Q was also a toxin by nature and it could also
have dangerous side effects, effects perhaps unheard of in the
Chinese experience.  The thought of thousands of people self-
medicating with Q was sobering.

At the same time, if Q did have the capabilities in-vivo that it
showed in vitro, a disaster of another type awaited.  Two and a
half years had already passed since its discovery, and its
development had proceeded in secret and at the glacially slow
pace of U. S. drug development.  How many more years would pass
slowly away while people died in ever-increasing numbers?  How
long would traditional methods take to determine the usefulness
of the drug?  Or how quickly could they develop credible data to
discourage its use, now that the genie was out of the bottle?

Project Inform decided to take action, following the very model
upon which the organization formed in 1985 - the development of
community-based treatment protocols and data gathering.  It was
critical to develop information on the safety or usefulness of Q
to guide or discourage community use.  We convened a team of
physicians and researchers who had knowledge of this class of
drugs,along with people from the patient community, attorneys,
activists and other interested parties.  Collectively, a protocol
was drawn up to treat 60 people in four groups.  The protocol was
reviewed by 7 community physicians, at least half a dozen
researchers, several lawyer~ and regulatory experts in 3 states,
and an uncounted number of community representatives and
potential patients.  Agreement was reached about the objectives
and design of a program which was scientifically comprehensive,
morally expedient, and completely ethical.  The protocol was in
keeping with Project Inform's original mission - the creation of
community-based research following a treatment model for
clinicians, rather than the research model of academics.  The
complex activity sheet which guided the program is shown in
Figure 1.

To ascertain the quality of the Chinese drug and to conduct
necessary animal toxicology studies, medical director Dr. Alan
Kevin established a relationship with the noted cancer research
center at the University of Nottingham in England.  Later, the
laboratory conducted follow-up studies to look for the
development of antibodies against Q in the patient's blood.  In
this and in many other regards, the PI study exceeded the
complexity and scientific sophistication of most other community
based programs.

The objectives are simply described:

* first and foremost, to treat patients who were failing
conventional therapy or who had exhausted their treatment
options;

* to learn from the experiences of these first courageous
patients by treating them under a fixed protocol and collecting
lab and clinical data as would be done in a research program;

* as much as possible, to make a preliminary evaluation of the
safety of using Chinese trichosanthin while gaining as much data
about its efficacy as possible; this data in turn would be used
to guide or dissuade community use of drug.

With these objectives and the design of the treatment protocol in
place, and the experiences of the pioneering Florida group to
guide us, the first patients were treated under the program in
the last week of May.  The groups consisted of a total of 19
people in San Francisco (under Dr. Larry Waites and Alan Levin),
17 in New York (under Dr. Barbara Starrett), and 15 in Los
Angeles (under Drs. Don Long and Paul Rothman).  In Florida, the
separate program already underway for two months began using our
case report forms to collect and report their data. Dr. Robert
Mayer and the group in Ft.  Lauderdale followed their own program
design, which addressed many variables not part of the program
followed at the other three centers.

Program Outcomes

A final assessment of the protocol outcomes will not be completed
for several more months, as participants will be followed for a
total of six months.  Reports of toxicity and preliminary reports
on efficacy, however, were made to the community in San Francisco
on September 19 and to the FDA in Washington on October 6.
Toxicity reports are considered reliable at this stage since
patients have already completed their scheduled administrations
of the drug.  Efficacy reports, however, are very preliminary and
cannot be considered definitive.

Toxicity

Most participants tolerated the drug quite well, with the vast
majority reporting only minor toxicities reminiscent of flu- like
symptoms.  More serious toxicity was noted in a small subset of
six participants.  The implications of the toxicity findings must
be stated up front.  Although we are not recommending that anyone
use the drug, Q should definitely not be used by the following
types of patients:

* people with very low T4 counts(less than 100, * people with any
evidence of HIV infection in the brain or nervous system * people
with active opportunistic infections * people who are severly
debilitated or near death

The reasons for this warning are evident in the toxicity
findings.

Minor toxicities were experienced to some degree by almost all,
although very few found the problems bad enough to warrant dose
reduction or drop-out.  The most common problems included mild
fevers lasting for up to 2 to 5 days muscle aches and pains,
joint pain and swelling various rashes, and some hives (only in
people who received intramuscular injections).  These symptoms
cleared with time after treatment with the strongest effects
occurring after the third treatment. These problems were not
serious enough to discourage use of the drug.

Six people also experienced a more serious form of side effect
best described as mental status change.  This ranged from brief
periods of confusion or disorientation, to reversible coma and
seizure at the extreme.  Although media reports have varied, as
have initial descriptions by medical personnel, the current
official breakdown is as follows:  one person experienced a
reversible coma; two experienced temporary seizures; three others
experienced periods of disorientation or confusion ranging from a
few hours to a week.

The patient who experienced coma awoke in 48 hours after
treatment with the steroid Decadron (commonly used in head
injuries).  Six days later, he aspirated (vomited and inhaled) in
his sleep and was not resuscitated in time to recover.  The cause
of aspiration is unclear; it may be related to the prior coma, to
any possible use of sleeping or pain medications or any other
medications, or even to digestive upset.  Some confusion exists
about the events at the hospital on the morning of his death, but
it appears that hospital staff believed the patient suffered
brain death as a result of lack of oxygen due to the aspiration.
Consequently, a recommendation was made to his family to withdraw
life support.  Contrary to early media reports, there is no
suggestion that this action was taken inappropriately.  The
family acted on medical advice and later sought, along with the
program physicians, to have an autopsy performed.  It is
unfortunate that the neither the hospital nor the coroner would
permit an autopsy.  Even though the drug would have cleared from
his body several days previously (the drug's half life is less
than 2 hours), physicians needed to know whether it played any
role in the cause of death.  Without the autopsy, we will never
know.

One patient who experienced a seizure and disorientation was
briefly hospitalized but released in 24 hours.  In subsequent
weeks, he rejoined program activities, testifying to others about
his experience.  He also repeatedly sought retreatment, but was
refused because of the doctor's concern about his initial
experience.  Approximately 6 weeks after his treatment, the
patient died of what his doctor felt were unrelated causes or
causes which preexisted his use of Compound Q. After the New York
Times printed a spectacularly inaccurate account of the
circumstances surrounding the patient's death, a firestorm of
controversy engulfed the treatment program and unfairly maligned
the highly respected New York physician conducting it.  A second
patient who suffered a seizure in San Francisco recovered without
incident.  The remaining 3 patients who suffered less severe
mental status change responded positively to treatment with
Decadron.

One patient in the "official" study of GLQ223 at San Francisco
General Hospital also suffered a coma, from which he has only
partially recovered.  In this instance, however, the patient was
not immediately treated with Decadron.  He remained semi-
comatose for more than 10 days before treatment with Decadron was
attempted, and awoke 48 hours later.

This mental status change was never an immediate result of
treatment, but occurred 24 to 60 hours later.  It always began
with mild confusion or disorientation, but in some instances
became more severe over time.  Treating patients with Decadron at
the first sign of disorientation, and continuing treatment for 72
hours, appears to keep the problem from worsening into coma or
seizure.  But no one can be certain of this without more
experience.

There were three key things learned in these incidents.  First,
the occurrence of mental status change was not related to the
dose used.  The problem occurred in some patients receiving only
10 micrograms (per kilogram of body weight) in the PI program,
and in the patient received 36 micrograms in the "official"
program.  Even the distinction between coma and mild confusion
did not appear to be dose related.  Instead, the factors which
predicted mental status change were the patients' T4 count and
their history of nervous system involvement with HIV.  The mean
(average) T4 count of patients who had a mental status change was
23, while in patients who didn't have the problem it was 169.
Also, 3 of 4 patients who received MRI (Magnetic Resonance
Imaging) brain scans prior to treatment showed evidence of HrV-
related problems in the brain.  Others were not tested.  Another
type of toxicity noted was more difficult to categorize since it
was infrequently and inconsistently seen.  In one center, two
patients with KS were believed to worsen, with spreading of
lesions.  This occurred in patients treated intramuscularly, an
approach abandoned and not used elsewhere because of the severity
of side effects.  When given intramuscularity, the drug appears
to remain in the system far longer than it needs to.  In other
centers, the response to KS was mixed, with no hard evidence of
either worsening or improving.  Two patients reported clearing of
minor lesions, but this is not well documented.

A last type of toxicity is one which is indirect.  While in the
body, trichosanthin is somewhat immunosuppressive for a short
period.  In the earliest patient groups, steroids were given
along with the trichosanthin to moderate expected side effects,
such as fever and muscle aches.  The combination of the
immunosuppressive effects of the drug, as well as those of the
steroids, may have worsened an existing opportunistic infection
in one patient.  Because of this, the program later switched to
the use of non-steroidal anti-inflammatory drugs, such as Motrin,
to moderate fever and muscle ache.

Summary, Toxicity:

In sum, the toxicity picture of Compound Q is mostly similar to
that reported in China, with the exception of the mental status
change which appears to be unique to HIV infection.  Because this
toxicity is potentially deadly, it argues against any form of
self-medication or self-experimentation with Q. Clearly, this
drug should only be administered in a sophisticated clinical
setting by experienced medical personnel.  Afterwards, patients
must remain under observation in some form for at least 60 hours,
and problems must be reported to medical professionals
immediately.  Patients with KS should avoid use of the drug until
a clearer picture emerges of its effect, as should anyone with
active opportunistic infections.  Despite these concerns,
however, the toxicity appears to be sufficiently manageable when
the drug is given in a proper medical setting by experienced
personnel and should not hinder its future development.
Unfortunately, critics of the drug, or the theory of AIDS it
represents, are already using the toxicity evidence gathered here
to condemn the drug.  We find this foolish, short-sighted, and
scientificallu dishonest.  In our belief, anyone expecting to
find a completely non-toxic, utterly natural treatment for AIDS
(which tastes good, too!) is engaged in magical thinking.  AIDS
is one of the most toxic and destructive diseases known, and it
works by destroying the body's ability to fend off the invader.
We reluctantly accept the notion that treating it, managing it,
or eventually curing it, will never be a piece of cake.

Efficacy

It is critical to put any findings of efficacy in perspective, as
there are several reasons that they must not be seen as
definitive or conclusive.  The data represent a snapshot in time,
not a final result, and is reported part-way through the program
using the latest data common to the centers.  It may improve or
worsen over time.  Also, the data lack a traditional control
group for comparison (although in some instances it is possible
to use the patients' medical histories as the control).  Another
limitation is that the data reported thus far only incorporates
part of the study groups.  It may not be possible to fairly
directly incorporate the Florida data, since the program design
there was different in very significant ways.  The data from the
Los Angeles arm has not been incorporated because case report
forms - the key study document - are not yet completed.  Thus, at
the time of this writing, the effficacy data primarily represents
the combined findings of San Francisco and New York, since these
groups operated in essentially the same fashion and submitted
completed data by deadline.  The Florida group has already
released a separate summary of their findings.  Finally, we must
remember that Phase 1 data is never conclusive.  It is typically
not statistically significant because of the lack of control
groups.

Yet, despite the concerns, there is some reason for confidence in
the findings.  While the markers are considered "soft," they all
point in same direction.  Clinical observations appear to support
and even extend the lab data.  The findings occurred primarily in
patients who were failing despite long-term AZT use, making this
a worst case analysis.  That a drug would have any effect at all
in such a circumstance is encouraging.  As much as possible, the
treatment program followed the conventions of good research:
close, elaborate follow-up, use of a single, central lab, and had
a very high degree of patient compliance.  In these regards, as
well as the lab numbers, the program outcome might be favorably
compared to the data submitted in the DDI Treatment IND
application.  Efficacy was measured in both anti-viral properties
as well as immune responses.  For antiviral activity, patients
were tracked with the p24 antigen test (Coulter Counter).
Because this test is not legal except in "official" research
programs in New York, the data presented is based on the San
Francisco arm.  All San Francisco patients were considered AZT
failures, most with active or high p24 values despite long-term
AZT use.  Data were collected weekly and then monthly.  At the
last data collection point (2 to 3 months after beginning
treatment),

8 of 14 patients with positive p24 showed a sustained drop,
averaging about 50% (remember, these numbers are generated
several weeks after the last treatment).

6 patients who had high p24 values at baseline (more than 100),
all 6 had a sustained drop averaging 67% (graph shown).

4 of the 4 patients who were p24 positive in Florida experienced
a sustained decline of about 50%.

The decline in many had been greater shortly after treatment, but
levels were edging back toward baseline at the late data point.
It appears that the higher the starting p24, the bigger the
benefits.  Some of the remaining patients also experienced
initial drops, but their counts had returned to baseline at the
last data collection point.

At least one critic has pointed out that AZT reduces p24 to
undetectable levels, at least for awhile,in some patients.What's
so good about these results, he asked?  What's good is that these
results occurred after 2 or three injections of a tiny amount of
fluid - not months of daily therapy.  Also, they occurred in
patients in whom AZT was already failing to control p24.

There was also some preliminary evidence of efficacy in T4
counts, although the degree of benefit varied both by the
starting health of the patient and by the dose of the drug used.
The T4 data are drawn exclusively from the New York and San
Francisco arms of the program.

Mean T4 counts were calculated at baseline and were again at the
latest data point all patients had in common, a period two months
after therapy began.  The results were as follows:

Compound Q - The Real Story


T-Cell Response, Group Means
Subgroup                 Baseline       Post Rx Chge.
A 11 S F        91      102     +12%
A 11 N Y        119     169     +42%
All starting > 100 T4   225     286     +27%
All starting < 100 T    427     33      +22%
All using low dose      58      88      +52%
All using high dose     160     183     +14%
High dose, > 100 T4     245     261     +7%
High dose, < 100 T4     33      66      +101%
Low dose, >10Q T4       182     342     +88%
Low dose, <100 T4       57      34      -19%

<<<There are 3 graphs showing:
        P24 antigen levels
        CD4 response 4 subgroups SF, NYC, All >100 CD4 all <100
CD4
        CD4 response, 4 subgroups, by dosage and low/high T4>>>


It is important to remember that these are changes in the mean T4
counts of the groups and subgroups.  Some individuals did better
than figures suggest, while other did not do as well.  A clear
majority, however, experienced gains rather than losses. Some
critics have pointed out that not all of these changes represent
clinically significant changes.  Whether or not this is the case,
they fail to note that this is the method - reporting of changes
in group means - by which the T4 impact of all other drugs, such
as AZT and DDI, is measured.  By this standard of comparison, Q
is doing very well at this stage.

The Florida group's separate findings showed an overall inc;ease
in percentage of T4 helper cells, but not an increase in the
total mean T4 counts.  Since this group represents many different
methods of administration and dosing schedules, it is more
difficult to interpret and is inherently less able to demonstrate
credible efficacy findings.  Nonetheless, in addition to
pioneering the treatment use of trichosanthin, this group
explored several important approaches to treatment from which all
other groups learned.

As might be expected from these data, improvements were also
noted in T4-T8 ratios (up 16% in SF, 43% in NY) and T8 levels
overall decreased (after an initial increase).  ESR
(sedimentation rates, an overall indication of inflammation or
infective activity) declined substantially - down 39% in SF, 15%
in NY. Beta2 microglobulin levels initially increased in most
patients, as would be expected if cell death were occurring, but
declined over time in the healthier patients. The New York group
showed a 34% drop in beta2, while the San Francisco group showed
a slight 10% increase.  Nearly all patients experienced a short
term increase in white blood count, with most patients have a
slight, sustained increase of less than 10% overall.

Clinical responses

In addition to lab marker improvements, physicians have reported
clinical improvements in many of the patients. Although such
measures are more subjective, they are perhaps more significant
to the HIV patient, who often finds his/her feelings at odds with
the lab data.  The most common clinical response, reported by a
majority of patients, was a marked and lasting increase in energy
levels.  A few participants have returned to work or full-time
school for the first time in years.  Others have reported
clearing of long-running minor OIs, such as hairy leukoplakia and
thrush (although such symptoms often worsened briefly shortly
after taking the drug).  In future programs, greater care will be
taken to measure functional levels, such as Karnofsky scores,
before and after treatment.

Efficacy summary

Although the data are only suggestive and inconclusive, they
appear to indicate the possibility of benefit for many types of
patients after using trichosanthin just three times.  All
benefits noted thus far seem temporary, with declines beginning
to show up 6 to 8 weeks after treatment.  The presence of
additional benefits from repeated, regular use, such as once a
month, or once per quarter, awaits further study.

The fact that any efficacy data emerged in a short treatment
protocol is in itself cause for hope.  Perhaps what is most
important about any possible benefits from trichosanthin is to
reflect upon the mechanism of its action.  Whatever it is doing,
it is reasonable to suspect that it is doing it by killing
infected cells.  That it can work at all by killing cells opens
up new horizons for AIDS research.  Whatever its benefits, they
should be additive to those of any other therapy.  Many possible
combination therapies are immediately suggested.

Two factors have previously given some researchers qualms about
the potential for using trichosanthin - the possibility of
allergic or anaphylactic reactions, and the development of
antibodies against the drug itself.  Either would seriously limit
the usefulness of the drug.  Both of these concerns have been
answered, at least partially.  No patient in our groups or in the
"official" study have so far experienced allergic or anaphylactic
reactions.  Also, work conducted by PI with the University of
Nottingham (U. K)has so far found only a single patient who  has
produced a mild antibody response to trichosanthin.  In this
instance, the patient has already been successfully retreated
without incident.

The Aftermath

On October 6,1989, PI and the treating physicians met with the
FDA in Washington for what all involved concluded to be a
remarkable meeting.  One senior FDA official privately called it
"day one of the revolution."  A senior executive of one of the
world's largest pharmaceutical firms (who attended) called it the
"most exciting - and most terrifying" meeting he had attended.
"Exciting" because it represented approaches to research that
many had long believed necessary; "terrifying" because of its
implications for business-as-usual in the pharmaceutical
industry.  Rather than the chastisements critics had called for
at the meeting, a respectful scientific discussion took place,
one which assumed and demonstrated integrity on all sides.  The
outcomes of this meeting, which we feel are very positive and
which break new ground, must await a final joint announcement.
But for now, we can say that both treatment and research with
trichosanthin will continue as long as the data and clinical
findings deem it appropriate.  And Project Inform will be an
active player in that process.

While this scenario continues to unfold, many patients will feel
caught in a terrible bind of wanting to use the drug as a last
resort, or as a bold first step.  Those who seek to use the
Chinese drug - without waiting for additional information,
unfortunate!y must be discouraged from doing so.  The risks are
high for the very type of patient who is likely to feel most
desperate to try something.  For those who fear for their lives
in the very short term, trichosanthin may never be a good options
it is so demanding of the patient's strength.  For those less
ill, other options should be exhausted first.  It makes little
sense for omeone who hasn't tried AZT to demand trichosanthin.

Dilemmas exist for people at all ends of the spectrum of HIV. It
is difficult to argue against the paint voiced by the sickest
patients that they have nothing left to lose.  It is easy to see
why healthy seropositives feel that the drug is unlikely to pose
them any great risk.  And those in the middle can convincingly
assert their right to try to stop the decline of the immune
system before they fall into a high risk category.  Yet these
arguments are generic to almost any new drug.  For now, we can
only say that the drug's benefits are not so well proven that
serious risks should be casually accepted in using it.  Yet this
is only an opinion.  Neither Project Inform - nor anyone else -
has the right to tell individuals what they can and cannot do,
what risks they can and cannot choose to accept.  We feel we have
already accomplished our primary goal, that of clarifying the
safety and risks of using Chinese  trichosanthin.  The risks are
very real, but probably limited to a certain class of patients.
The benefits are as yet more ephemeral, but enticing.  whatever
personal decision individuals choose to make, a few points are
clear:

Trichosanthin should never be self-administered or given by
anyone less than fully qualified medical personnel.  In the PI
program, this meant an anesthesiologist to set the IV, a
resuscitation specialist and kit, a bee-sting kit and experience
in using it, at least one primary physician, and a watchful
companion for at least 60 hours.

The drug is very dangerous for people with T4 counts below SO (or
even below 100), especially in the presence of even the slightest
evidence of HIV involvement in the brain or nervous system.

People on or near the deathbed have little chance of being helped
by trichosanthin, but a good chance of being harmed by it (the
same might be said about AZT, however).

We don't yet know the best way to use the drug, to harness its
cell killing powers.  Although the PI program has gathered more
data on this than anyone, it is incomplete.

Despite these considerations, there is a substantial subset of
people who have used the drug who report strong and lasting
improvements.  Their experiences are verified both by their lab
numbers and the judgments of their physicians.  These are tough,
individual decisions and, once fully informed, we must be willing
to entrust others with their own destinies. Trichosanthin is far
from a perfect option, but it shares imperfection with all of the
other alternatives.  Whether it is an appropriate alternative for
anyone at this stage of its development, or ever will be, remains
a matter of personal choice.

*****

Informed Consent

An essential part of the Project Inform trichosanthin treatment
protocol was a level of informed consent that even critics
acknowledged to be unprecedented.  Many patients, physicians, and
(to our surprise) regulatory officials have admitted to us that
the traditional informed consent and review process does little
except increase bureaucratic delays and protect research
institutions, while often leaving the patients to fend for
themselves.  Patients complain that the informed consent process
is little more than a signature on a poorly understood and
awkwardly-written document, signed blindly in a hasty and
desperate effort to secure access to a treatment otherwise
unavailable.  It is not unusual for such informed consent
documents to overlook key side effects of drugs (as occurred in
the suramin disaster of 1986).  Under the traditional system,
once a study has been approved by a nameless, faceless
Institutional Review Board, and once the patient has signed a
poorly understood consent document, all rights are given up.

The informed consent process established by attorneys working
with PI differed in key ways.  The consent document, a lengthy
but simply written piece, ran 13 pages and was given to patients
at least 24 hours prior to signing.  Next, the patient selected a
personal friend or witness to join him/her at a video-taped
consent discussion.  This half hour discussion included the
patient, the witness, the treating physician, and a "patient
advocate" who was typically an attorney and who led the
discussion.  The advocate's duty was to make sure that the
patient understood the risks, the lack of any proven benefits,
and the availability of other treatments.  The patient's
experience with other treatments and the reason for failure were
documented.  The patient's witness was present so that all might
determine that the patient was of sound mind in making the
decision to seek treatment with trichosanthin.  When all points
were clear, and after the advocate challenged the patient on each
keypoint, the patient made a closing statement to his/her loved
ones or relatives, explaining why he/she was doing this.  As any
patient who has gone through this process can attest, their
consent was, perhaps for the first time, true informed.

Consent, however, did not end with the signing and video- taping.
Instead, each time a significant adverse event happened to
anyone, all the patients in the program were notified, typically
within 24 hours, and invited to reconsider their participation.
This is in stark contrast to the "official" "approved" model, in
which such data are discussed and kept secret by data safety
monitoring boards, IRBs, and researchers. A terrifying example of
this was the 1986 suramin study.  Long after several patients had
died from complications of the drug, others were still being
urged to continue taking it, but weren't being told of the newly
understood risks.  In the recent AZT seropositives study,
"informed consent" erroneously meant telling patients that there
was no need for PCP prophylaxis, that AZT itself would do the job
(PCP prophylaxis was finally added in February of 1989, almost a
year and half after the start of the study).

As new experimental treatments become more widely available under
such programs as parallel track, it will critical that new and
better approaches to informed consent be used.  We believe that
the steps taken in the trichosanthin treatment protocol, while
not perfect, point in the proper direction.  It is not enough to
sign a complex piece of paper, nor is it enough to think that
some nameless, faceless institutional review board will look
after your rights.  The patient him or herself must be better
informed, and a determination should be made that true
understanding exists.  Education, not bureaucracy, is the best
form of consumer protection.

============================================================
Project Inform expresses its deepest gratitude for the support,
both personal and financial given during the trichosanthin
program by our members and constituents.  The program was costly
(but a fraction of the cost of standard research), but our
supporters didn't flinch.

Innovative work such as this cannot be done without your
assistance.  Your contributions truly make a difference.
============================================================

*****

Q-lnduced Mental Status Change

One of the most intriguing, and most discouraging learnings of
the Project Inform trichosanthin treatment program was the
discovery of mental status changes ranging from disorientation to
coma.  Most certainly, these events, however infrequent, are
related to the effects of HIV on the brain and nervous system.
Researchers studying the problem hope that this new knowledge
will lead to a better understanding of AIDS dementia.

There are two possible causes of the mental status change.  The
first and most obvious is the possibility that Q is directly
killing infected cells in the brain.  HIV infection comes to the
brain in a form of macrophage called microglial cells.  These
cells are transient, moving through the brain, and are not part
of its permanent structure.  While in the brain, they provide
nutrients and act to some degree as insulators.  Thus, it is
theorized that if many infected glial cells are killed at once,
some disruption of brain activity would be expected, accounting
for the mental status change.  This explanation would require
that Q cross the blood/brain barrier, which is uncertain because
of the fairly large size of the molecule.  The blood/brain
barrier of HIV-infected people, however, is believed to be
seriously weakened, making more possible that the drug could
cross over.  If this explanation is correct, the problem might be
solved by treating slowly at very low doses, thus more gradually
clearing out the infected cells while causing less disruption.
This theory is consistent with the finding of some patients that
their mental acuity improved substantially after treatment.

The second theory is that the problem is "factor mediated," in
other words, it is caused by some substance or "factor" being
released in the blood.  There is growing evidence that AIDS
dementia itself is caused by a factor, called a cytokine, which
is being released by infected cells.  When this cytokine reaches
the brain, it apparently disrupts neurotransmitter
(electrochemical) activity, thus causing dementia or mental
status change.  At the extreme, it causes coma, just as we have
seen with Q. Research at San Francisco General Hospital is
underway to identify this substance and then see if it is perhaps
being released by dying cells after treatment with Q. If so, slow
gradual treatment may also help, as would the development of an
antidote to the substance itself.

*****

AZT News:  The Final Chapter?

In recent months, new studies on the efficacy of AZT have been
presented both by government scientists and private researchers.
The conclusions reached by the new studies have profound
importance but sound remarkably familiar to people who have
previously subscribed to the Basic Message of Project Inform.  It
is still too early, however, to say that we have the final word
on AZT use.  The three key studies reported:  ( 1 ) the benefits
of AZT for people with early ARC symptoms and having between 200
and 500 T4 helper cells; (2) the benefits of AZT in healthy
asymptomatics with fewer than 500 T4 helper cells, and (3) the
impact of AZT on the development of AIDS dementia in a long- term
Dutch study.  Since these studies have been reported on in the
media and in most AIDS news sources, and because the data has not
yet been published, we will only briefly discuss the primary
findings and focus instead on the practical implications and the
questions which remain in their wake.  In a fourth and very
important study, also not yet published, new data was reported
which confirmed for the first time that lower doses of AZT may be
just as effective as the higher ones in common use.

Primary Findings

Study 1:  A placebo-controlled study of AZT in 713 people with
ARC was conducted by the National Institute of Allergy and
Infectious Diseases (NIAID).  Volunteers were required to have
one or two ARC symptoms and a T4 helper cell count between 200
and 500.  The most important benefit noted after two years was a
lower incidence of progression to AIDS among those who received
the real drug.  Some 36 people in the placebo group progressed to
AIDS, as compared to 14 receiving AZT.  Few other details have
been released since the study outcome was announced in a press
release, rather than in a completed journal article. While some
have criticized NIAID for this, we support their efforts to
release important news without waiting the extra 6 months or more
needed for acceptance and printing of a completed journal
article.

Additional information about the incidences and severity of
opportunistic infections, the impact on T-helper cells and p24
antigen levels, as well as data on other key parameters, would be
helpful and should be forthcoming.  The bottom line, however,
seems clear:  AZT significantly reduces the progression to AIDS
when used in early intervention by people with minor symptoms of
ARC. This should surprise no one.

This study also reported a far lower incidence of side effects
from AZT in this healthier patient group.  As PI has pointed out
for more than 2 years now, reports of the most serious AZT side
effects have always been based on the experiences of late-stage
AIDS patients, in whom nearly 50% have shown significant side
effects.  Most physicians have long noted that side effects were
much less severe in healthier patients, a point well established
in even the earliest AZT studies.  In this study, significant
side effects were noted in less than 5% of the patients receiving
AZT.

Study 2:  An arm of the giant, placebo-controlled AZT
seropositives study, which is following nearly 3000 healthy
people with HIV but no symptoms, was brought to a halt by the
Data Safety and Monitoring Board which controls the study.  As in
the early study of AZT with AIDS patients, the Board ended the
study early when it found a statistically significant advantage
for people receiving real drug.  Even fewer side effects were
seen from AZT in this study, even though half of those on the
drug were receiving a higher dose ( 1500 mg.  per day) than had
been used previously.  Neither this group, nor one receiving 500
mg.  of AZT per day, experienced any greater level of side
effects than the placebo group.  The sole exception to this was
minor nausea, which occurred slightly more often among those
receiving real AZT.

Like the previous study, results were announced in a press
conference, leading to the same criticism.  The insistence on
awaiting acceptance of a journal article would have added at
least 6 months to the process - an unacceptable delay in the
context of an infectious, often fatal epidemic.

Other controversies exist over this study, principally whether or
not the trial might have been terminated too early (it sounds
strange indeed to hear AIDS activists wondering whether things
should go slower).  Skeptics question whether the advantage for
AZT recipients would hold up over a longer period.  Still others
contend that the advantage for AZT was demonstrated only during a
period of the study in which preventive treatment against PCP was
not yet permitted.  They argue that the benefit preventing
progression to AIDS - might have been achieved less expensively
and with less risk of side effects.

Study 3:  This important research from Dutch scientists suggests
that continuous AZT use begun early in HIV infection may
completely prevent the occurrence of AIDS-related dementia. While
not absolutely conclusive in this regard, the Dutch study at
least demonstrates a dramatic and clear advantage against the
development of dementia in patients who used AZT early on.

Study 4:  This research, reported but not yet published by Dr.
Margaret Fischl of Miami, seemed to show that a 600 mg.  daily
dose of AZT was just as effective in prolonging survival as the
higher, 1200 mg.  recommended for the last few years.  While this
comes again as no surprise to community physicians (and Project
Inform), it is extremely important that hard data from rigidly
controlled studies now confirms it.  A previous French study drew
similar conclusions last year.  New labeling indications will be
required now, which will have the effect of putting the cost of
AZT in half for those who weren't already following this path.  A
low dose AZT regimen, using only 500 mg.  daily, has already been
accepted as a criteria in the new studies of DDI. Physicians who
have long advocated lower dose AZT are now quick to point out
that many patients thrive on as little as 300 mg.  per day,
although this has not yet been confirmed by hard evidence.
Certainly, doses this low are already being used in studies which
combine AZT use with other drugs, such as alpha interferon.  The
message of this is not that people who are doing well on full
dose AZT must immediately switch to lower doses, but that those
who could not tolerate 1200 mg.  should try lower doses before
abandoning the drug altogether.  Whether there is an advantage in
switching to lower doses is less clear, but there is at least
some suggestion that the lower doses are less immuno-suppressive
and may thus sustain T-cell increases longer than the high dose.

Implications for Use

PI has long advocated the strategies implied by these findings.
Common sense and logic always suggested that if AZT diminished
viral levels in the sickest patients, and its side effects were
less severe in healthier ones, then it was likely that early
intervention would work.  For those who were willing, in the face
of a life threatening epidemic, to act on the dictates of common
sense without waiting for hard proof, the benefits of early
intervention became available in 1987.  For those who needed the
hard proof, it now stands before them.  Great credit must be
given to team of the researchers who did the hard work of proving
the argument for ear!y intervention -without their efforts and
determination, the debate would rage endlessly while the death
toll continued to rise.  But credit must also be given to
physicians and researchers who saw that early intervention was a
rational, ff unproven, course from the beginning.  Some who
argued on its behalf in 1987 and 1988 were unfairly accused of
selling false hope or overmedicating their patients for profit.
Must this be the price paid for challenging medical orthodoxy,
even in times of plague?  Time has exonerated the foresight of
these pioneers, but it doesn't always correct the damage done
their reputations and spirit.

As of fall 1989, clinical trials have demonstrated benefits from
AZT use for the following Hiv infected groups:

* People with AIDS
* People with symptoms of ARC or who have fewer than 200 T4
helper cells
* People with minor symptoms, regardless of
T4 counts
* People without symptoms but who have fewer than 500 T4 helper
cells


The only HIV-infected group for whom AZT is not yet formally
recommended are healthy people without symptoms of any kind with
greater than 500 T4 helper cells.  This group is still under
study in the remaining arm of the large seropositives study.
This does not mean, however, that there is any evidence which
suggests that such people should not begin antiviral treatment.
Instead, it merely points out that the benefits of doing so have
not yet been proven in the study.  It was always expected that it
would take longer to prove benefits in this group since the
patients' good health makes its difficult to tell whether a
treatment is working.  The same logic which suggested broad AZT
use before clinical studies proved its value, today suggests that
even healthy asymptomatics with high T4 counts may benefit from
treatment.

For many, the question now is whether to begin early intervention
simply on the basis of being seropositive.  At the very least, it
is one rationally supportable course of action, perhaps more so
than the opposite view.  To some, the reasoning is simple:  if a
potentially lethal virus is slowly destroying your immune system,
doesn't it make sense to hinder its activity, even if the
infection isn't yet making one feel ill? This view holds up as
long as the side effects of early treatment use are less harmful
than the gradual decline of the immune system common to HIV
infection.  One might ask:  just how much immune system capacity
do you wish to lose, perhaps permanently, before doing something
about it?  The current evidence demonstrates that AZT side
effects are minimal with healthy people.  Still, only completion
of the on-going clinical trial will produce a conclusive answer.
In the meantime, each individual must make a choice he or she can
feel comfortable with.

Remaining Questions

Despite the news these findings bring for clinical use,
legitimate questions remain.  The questions, and an attempt to
answer them, follows.

Does the fact of AZT resistance suggest that despite these
finding, it might still be better to delay AZT use untill  a late
stage of AIDS or ARC is reached?  Some physicians believe this is
the case, arguing that since AZT only works for a limited time,
it's still best to save it for when you need it most.  Although
well-intentioned and rational, this argument may overlook three
key facts:  (l) new and better antivirals are already coming to
market, so alternative antivirals will almost certainly be
available later if needed; (2) by using AZT now, many more people
simply won't progress to the point at which AZT becomes critical,
and (3) the assumptlon that AZT only works for a limited time is
based on the experiences of later stage AIDS patients.  The
duration of effectiveness in healthier people is still unknown,
and a good case can already be made that it will be useful for
longer than it is in AIDS patients.

Some researchers who have been right about just about everything
else in the epidemic argue that the most reasonable strategy
against HIV, given today's medicines, is to slow the progressive
activity of the virus and preserve as much of the immune system
as possible.  Letting I IIV run rampant in the body until some
arbitrary level of possibly irreversible destruction is reached,
such as 200 T4 cells, just doesn't make sense.  This view is
bolstered by the growing concern that immune function may not be
easily restored once key markers falls into seriously deficient
territory.

Couldn't progression to AIDS be slowed less expensively for the
majority of people simply by the use of preventive medicine
against PCP?  On the surface, this seems to make sense since PCP
has previously accounted for more than 60% of new cases of AIDS.
Government scientists point out that this view again overlooks a
key fact:  PCP prophylaxis prevents AIDS only by delaying the
onset of pneumocystis, while permitting continued degradation of
the immune system as well as the onset of other opportunistic
infections (which account for up to 40% of the cases of AIDS).
AZT prevents AIDS by slowing the decline of the immune system,
which should have a broader overall impact.  The best solution
includes both approaches.

Isn't is possible that long-term AZT use might cause side effects
which haven't yet been discovered?  This view argues that long-
term AZT use, even if beneficial for a few years, might result in
cumulative or long-term side effects, such as suppressed or
destroyed bone-marrow activity.  While this is not impossible, it
fails to acknowledge the problems associated with not using AZT -
continued destruction of the immune system.  No one argues that
long-term AZT use is a perfect solution - only that the evidence
says the odds are in favor of those who use it.  Any possible
unknowns of long-term AZT use must be balanced against the well-
known decline of the immune system and decreased survival rates
which occurs without it.  On balance, it appears that using AZT
presents fewer risks than not using it, though neither choice is
perfect.  It's important to remember also that people will not go
on using AZT indefinitely,with crossovers to new drugs such as
DDI, DDC, D4T, AZDU, or others becoming increasingly likely.

Doesn't the evidence suggest that some people with HIV win never
become ill?  If so, why risk messing things up?  This argument
has been fueled lately by some off-hand remarks by AIDS scientist
Robert Gallo, which are often quoted out of context.  Gallo said
that a significant percentage of people with HIV will not develop
AIDS.  Other researchers have pointed out that Gallo is speaking
out of his field here. Epidemiologists, which he is not, are the
ones who study the matter of HIV progression in groups of people.
They continue to report that more than 50% progress to AIDS
within 10 years of infection, and predict that a much higher
percentage will reach end state disease within 16 years - if
untreated.  The part of Gallo's remarks which are typically left
unquoted is his admonition that the odds for any individual are
in favor of progression to AIDS (with out treatment).  Gallo went
on to say that he believed it appropriate to begin AZT treatment
the minute a person knew he/she was infected.

While it is true that some people seem to show little decline of
immunity even after 10 years of HIV infection, they are a small
minority.  It makes little sense to gamble that you will be one
of the lucky ones.

Is it reallly worth the trouble of treating hundreds,if not
thousands of seropositives with AZT just to prevent a small
number from progressing to AIDS?  Just ask one of those who was
helped.  This is perhaps the most callous argument of all.  It
suggests that this is all a game of numbers and money, not human
lives.  It is based on a short term observation of the study with
asymptomatic patients, and completely overlooks the longer-term
picture.  Each person who can be kept from progressing to AIDS
for an extra year or so is a person who's life may be spared
forever as better treatments become available.  Since data now
shows that this can be done without unacceptable risk of side
effects, it is our job, our moral duty, to preserve each and
every last person for as long as we can.

Isn't the call for early intervention with the poisonous AZT all
part of a govemment plot, a secret plan of genocide designed to
kill gay people, IV drug users, and all people of color.  Simply
put, no. Our enemies aren't that effective.  While no doubt there
are some who secretly wish for such a plan, there is no credible
evidence that one is underway.  The AZT data comes from
researchers and physicians whose findings have proven true over
the years.  In fact, some of the scientists involved are members
of the risk groups the plot is supposedly killing.  AZT is not a
poison, and the government is not engaged in any widescale plan
to kill us all.  This is simply paranoid thinking.Those who make
such charges have failed over the years to demonstrate coherent
evidence to prove their case.  PI has followed and studied each
new conspiracy theory over the years and so far finds all of them
to be based on boundless assumptions, wild projections,
misinformation, and an appalling lack of factual evidence.  Such
hysteria, while perhaps well-meaning, surfaces in every major
crisis and natural disaster.  True, society has failed to respond
effectively to the crisis, but conscious genocide is simply not
on the agenda.

Conclusion

The new evidence on AZT use is good news,but news only to those
who haven't been paying attention for the last 3 years.  Now that
the hard evidence has been presented,, there is little room left
for the voices which continue to rail against AZT use.  As new
treatments such as DDI are added to the arsenal, there will be no
room left at all.  We must, however, remain vigilant in the fight
to develop new and better treatments.  AZT and most other current
treatments are severe!y limited in their capabilities.  Society
cannot rest until we have developed the ability to truly reverse
the course of HIV infection, ff not eliminate it altogether.

This latest information should (but won't) sound the death knell
for the views of those who have bitterly opposed AZT for the last
3 years.  These views have been repeatedly discredited in every
study conducted.  While the debate raged, critics could be
forgiven by the thousands who were mislead into forsaking some of
their precious survival time.  While AZT will never be the right
drug for everyone and will allways be a subject of personal
choice, continued promotion by community leaders of the
unbalanced view that "AZT is poison" must be seen for what it is
- a desperate attempt to change to long- discredited views.  Such
beliefs, now endangering the lives of our brothers and sisters,
is more the product of political and personal positioning than
sound medical reasoning.  It must stop AZT is not a perfect drug,
but it has extended the lives of tens of thousands of those
stricken with HIV.  It has been given every possible chance to
fail in rigid, placebo-controlled studies and in the challenge of
clinical practice .  It has withstood the tests of time and its
critics.

*****

The Road to Parallel Track

A special issue report

Parallel Track is a new word for a concept that has been promoted
by AIDS activists for several years.  It is an administrative
process by which promising drugs maybe released for treatment use
without waiting for the completion of research studies.
"Parallel track" proposes that research studies of a drug will
proceed on one track, while the drug is also used for treatment
purposes, outside of the research, on a separate, parallel track.
Think of it as two trains running side by side, one research, one
treatment use.

This is a key change in government thinking, namely that it is
possible to release drugs for treatment use without interfering
with clinical trials.  Previously, most regulators believed it
was necessary to prohibit distribution of experimental drugs in
order to guaranty that patients would sign up for clinical
studies.  FDA and others reasoned that if people could get a new
drug any other way, they wouldn't sign up for studies, especially
if a placebo was used.  Once officials accepted the notion that
people joined studies for other reasons, and that distribution
could be managed in a way that protected the studies, the concept
of "parallel track" became plausible.

The name and some of the initial government movement were
contributed by Dr. Anthony Fauci of the NIH, but the road to
parallel track was paved with the hard work of many activists,
patients, physicians, political workers, attorneys, and people
within the government.  Project Inform has contributed to this
effort since 1986.  Other key players were ACT-UP (with major
contributions from ACT-UP New York), the government offices and
staffs of Congresswoman Nancy Pelosi, Congressman Henry Waxman,
and Senator Ted Kennedy, AAPB, and dozens of people whose names
seldom show up in the spotlight.  While some individuals and
groups have made especially important contributions, parallel
track is truly the result of a team effort.

Despite the current inclination to declare victory, it is
important to note that parallel track is so far only a concept
Not one person has received treatment under a parallel track
program, and the present DDI distribution is so restrictive that
no one should confuse it with parallel track.  Key issues are
still being worked out in an ad hoc Parallel Track committee now
meeting under the direction of Dr. Jim Allen of the Department of
Health and Human Services.  The most challenging aspect is to
make the benefits of parallel track available to all,not just the
well-insured orthe well- connected.  Achieving this lofty goal
will require the continued collaboration of all parties.  This is
not a time for self- congratulation, chest-pounding oratory, or
escalating demands. Like all negotiations, the final outcome will
be the result of honest dialogue and mutual respect.

*****

Treatment Strategy
Seropositive Y/N ?

Testing of - p24 anti-gen/body  - T4  - beta2 microgobulin

Anti-viral treatment

T-4 continuous trend

Lowest range (under 200) Preventatives for PCP

Low range (200-500) Immune modulators

High range (over 500) Monitor quarterly

*****

Using the PI Hotline

by Larry Tate

In the first four months of 1989, Project Inform's treatment
hotline handled about 18,000 calls.  To help you make the best
use of the hotline, we'd like to say something about who we are,
what we can do and can't do.

To begin with, the hotline is staffed entirely by volunteers.
Many of us have AIDS, ARC, or HIV; others are closely involved
with those who do.  We have a whole range of personal
experiences, opinions, and anecdotal information just as you do.

But the most important thing we have is training in the use of
the resources in the PI office.  Among other things, these
resources include:

* Our own fact sheets, newsletters, bulletins, memos, hotline
updates.

* Other treatment newsletters, such as AIDS Treatment News, BETA,
and GMHC's Treatment Issues.

* A forms bin stocked with the best and most current articles on
treatments we're often asked about.  These are available to us
under the name of particular treatments, such as Foscarnet, and
under listings for specific infections, such as MAI and CMV.

* Files on most known treatments and infections, filled with
copies of articles mostly from medical journals, but also from
magazines, newspapers, or any other source which provides
information.

* The AMFAR Directory, the CDC AIDS Weekty, the National AIDS
Network directory, and miscellaneous publications from different
agencies and foundations.

* Our own clinical trials binder .

* Binders with various referral numbers for buyers' clubs, drug
companies, PWA groups, other hotlines.

* A room filled with late notices taped to the walls, written on
the blackboard and bulletin board, floating around the desks,
sitting in bins, etc.

The goal of the PI hotline volunteers is to find, in all these
resources, the information you want and to get it to you, over
the phone or in the mail.  Although we try to do our best, this
isn't allways possible, for the following reasons:

* Sometimes we have the information but can't find it quickly.
Though we hope all these resources will at some point be entered
and available on a computer, usable by hotline operators, they
aren't now and we do miss things from time to time.  Sorry -
nobody's perfect.

* Sometimes we don't have the information because it's too new.
There's so much going on, it takes time for us to catch up with
some things just coming into use.  You can help by telling us
about treatments we should know about, and sending us any
information you think we should have.  (And not just useful
treatments:  we're just as concerned with knowing about any
likely rip-offs or harmful products as well, so we know what to
say when others ask about them.  The uncertainty of AIDS creates
big opportunities for deliberate fraud as well as misguided
quackery.)

* Sometimes we don't have the information because it doesn't
exist, or we have no way of verifying it.  There are many alleged
treatments for which great claims are made, but which are
documented poorly or not at all.  We may tell you we have nothing
worth sending, or may send something with a disclaimer saying we
don't vouch for the contents.

* Sometimes the information is outside our field.  We deal
primarily with treatments, pharmaceutical treatments in
particular.  We are less well covered on holistic treatments,
part}y because as a group they are less well documented. Although
we don't deliberately discount them, we admit they are better
covered elsewhere.  We also track related issues, such as
regulatory and research policies and insurance matters.  Often,
if we don't have something, we can suggest other resources.
Still, sometimes we just can't help someone.

Because we're based in San Francisco, we have a wider range of
information about local Northern California resources than about
other areas.  If there is an AIDS agency near you, they'll often
know more about your local resources than we will.  They should.

* Sometimes the information requested is something only a doctor
or researcher should be expected to interpret.  We're not
physicians, nor can we promise to have one on call, and very
often even a physician couldn't or shouldn't say what to do
without a personal examination.  (Occasionally, in emergencies,
we might try, as an aid to doctors, to investigate some
particular medical issue.  But this is rare, and we're not really
set up to do it.)  We know not all doctors are up to speed on
AIDS issues, especially when it is only a small part of their
practice.  But we cannot be expected to provide a "second
opinion."  If a real problem exists, we can usually refer you or
your doctor to medical authorities.

* Sometimes we're asked questions we have no right to answer,
such as:  what treament should I try?  What should I do to get
better.  Should I change doctors?  Is my doctor wrong?  If you've
read our treatment strategy, fact sheets, and newsletter - and
keep up with most of what's written - you may know as much as we
do.  If we knew what was best for you,we'd tell you.The truth
is,nobody can yet tell you what's best in each individual
situation.  AIDS and HIV vary widely from one person to the next.
(Sometimes we may make a specific suggestion, such as using
aerosol pentamidine if your T-cell count is under 200; but that's
unusual and limited to what we call our "Basic Strategy.")

* Sometimes we're asked questions for which there is no real
answer.  The typical one is:  what's new?  Anybody who answers
this is giving you their opinion, nothing more.  It's okay to ask
for updates on particular drugs; there are always developments
between newsletters, and they don't always reach the media.  But,
most of the time, the answer to "What's new on drug X?" is:
Nothing.

* Sometimes what our callers need most is not information but
counselling.  We know some people may be in tough situations
without much in the way of support (we've been there too), and we
try to listen sympathetically.  But we're not trained to be
counsellors, and it's not a good idea to expect it of us.

* Sometimes we can't answer because we don't have enough to go
on.  If you heard about some new drug on TV that morning, but you
don't know what it's called or what it's supposed to do, neither
do we.  Also, by now you know how inaccurate media reports on
AIDS can be, so don't be overly alarmed with us if we can't back
up everything that's said on TV or in the newspapers.

* And, of course, sometimes we're asked questions whose answers
are too large and depressing for anybody to answer:  Why are
things moving so slowly?  Why can't I get access to the
treattnent I need?  Why won't anybody pay for it?  Doesn't
anybody care?  And so on.  We're often asking the very same
questions.

A technical note:

There are six lines and not more than four volunteers on a shift.
If you get put on hold and forgotten, or get a busy signal or a
machine, try again.  If we sometimes rush you, forgive us.  It's
because there are several calls waiting, little lights blinking
at us, and six people in the office wanting to talk to someone.
If you just want to put a name on the mailing list, check or
change an address, or ask for a particular fact sheet, it's safe
to leave messages on the machines outside of hotline hours; the
tapes are transcribed daily.

And finally, a personal note:

Working on the hotline is challenging and demanding.  We do it on
our own time without pay.  And because PI is a small organization
with minimal staff, we do it without the strokes, recognition,
and support that might come from a larger, government-funded
organization.  Most of us find the work very satisfying.  It
provides a chance for us to make a contribution, and perhaps to
get our minds off our own woes in the epidemic. We try to do our
best.  If we fail you in some way, we apologize.  Because PI is a
national organization with a high profile, few people realize how
small and under funded we really are.  We are but three paid
staff members and a crew of 70 volunteers in a few small rooms in
old building full of community service organizations.  Most of
our volunteers are otherwise employed and/or not always in the
best of health.  The paid staff members are drastically
overworked for their minimal salaries, and in major areas where
we need paid staff, we have instead a few courageous and
determined volunteers trying to respond to the most urgent needs,
to keep us going for the time being.  If there is AIDS gravy
train   this isn't it.  We receive no government funds of any
kind, support from only a few key (and deeply appreciated)
foundations, no grants or help from larger AIDS organizations,
and no celebrity or high society funding.  But we believe
absolutely in the mission of this organization, and only wish we
had the facilities to do our jobs better.  We hope that you
understand our commitment as well as our limitations.  We are
deeply grateful for the support given directly by the community,
and do our best to put what we receive directly back into
services.  We're in this together.

*****

Clinical Trials:  Evaluating, Choosing, Entering

by David Glassberg

With the coming of DDI, the issue of clinical trials is quickly
becoming a key question on the minds of many people.  More than
two thousand people will be asked to participate in studies of
the drug, while thousands more may be able to get the drug in
special treatment programs.  As never before, making decisions
about clinical research programs has become a part of our lives.
An increasing number of our hotline calls deal with such
questions as "Should I join a clinical trial?  Which one?  What
am I getting in to?  How do I join one?  What are my options?
Before it can be sold by prescription, any drug has to be
licensed by the Food and Drug Administration (FDA) in order to
prove its safety and effectiveness.  After a drug is evaluated in
the lab and then in animals, experimental testing on humans may
be permitted.  To do this, FDA grants a manufacturer IND
(Investigational New Drug) status, which allows the sponsor to
conduct human studies.  This human or clinical testing is
performed in three phases.  Phase 1 evaluates the drug's
potential toxicity or side effects on a small number of patients,
while also attempting to determine the proper dose to use.  Phase
1 studies, however, aren't perfect in detecting toxicities.  For
example, AZTs bone marrow toxicity was not discovered until after
it was used by more people with varying degrees of health and
immune status in Phase 2 studies.

If a drug is well tolerated, Phase 2 testing is begun using a
larger number of patients (from as few as 200-300 to as many as a
few thousand).  These studies are designed to determine the
drug's effectiveness.  Sometimes, preliminary indications of
efficacy are found during Phase 1 testing, but they must still be
confirmed by Phase 2 studies.  AZT and DDI, for example, both
showed efficacy in Phase 1,while CD$ did not.  All three,
however, went on to Phase 2 testing.  Under new rules created in
1988, it is possible to license a drug at the end of Phase 2
testing, although this is not normally the case.

Phase 3, called confirmatory testing, uses larger numbers of
patients to confirm earlier efficacy studies and identify low-
incidence adverse reactions.  Together, these three phases can
easily take 5 years, at which point the drug may then receive a
FDA final approval which allows the drug to me marketed and
available to physicians by prescription.  When testing is
completed, the manufacturer submits an NDA (New Drug
Application), which - if approved gives it the license to sell
the drug.

Along the way between the three phases of research, every aspect
of study design must be approved by FDA.  Months typically go by
while papers and proposals fly back and forth between FDA and the
sponsor.  When studies are completed, it often takes several more
months to analyze the data, and more months for FDA to agree or
disagree with the analysis.  A typical data submission to FDA on
a new drug may contain tens of thousands of pages of material.
This is one of the reasons why its takes so incredibly long to
get a new drug out.

Under new rules created in 1987, FDA can grant a "Treatment IND"
for drugs that have proven safe and have shown some efficacy
during Phase 2 trials.  AZT was given a Treatment IND at the end
of its Phase 2 testing.  The Treatment IND was designed to
provide faster access to promising treatments for life
threatening diseases.  In practice, it hasn't always done so due
to conservative voices in the FDA who have traditionally placed
safety above all other considerations, even in the face of a
national health crisis.  People who desperately need new
treatments are still denied access.

In recent months, continued pressure by AIDS Activists, with
Project Inform on the front lines, has resulted in a rethinking
of these issues and has created a new concept called the
"parallel track" (described elsewhere in this issue).  Because of
the successful negotiations held in Washington this year, a
Treatment IND has now been granted for a drug, DDI, at the end of
Phase 1 testing for the first time.  In addition, thousands of
people will have early access to this drug in a compassionate use
program.  The implementation of these programs fulfills a
longtime PI goal of letting the people who are sick, not
bureaucrats, determine what treatments they can use.

Clinical Trial Enrollment

You can volunteer in any of the three phases of clinical trials.
First, you must know the trials in your local area. Clinical
trials (most commonly Phase 1 and sometimes Phase 2) may require
a short stay at a research clinic or hospital to monitor you for
any toxic reactions.  If you can't find a clinical trial you are
interested in your local area, then you may have to relocate to
another city.  To locate trials for HIV infection you can contact
the following organizations:

1.  National Institute of Health Clinical Trials Info.  Iine l-
800-TRIALS-l.  This number is for NIH sponsored trials only.

2.  American Foundation for AIDS Research (AMFAR) AIDS/HIV
Experimental Treatment Directory.  (212)719-0033 1515 Broadway
Suite 3601, New York, New York 10036-8901.  This quarterly
publication is FREE to PWAs/PWARCs and contains updates on drug
trials status, dosages, how the drug is administered and where
trials are being conducted, including a geographical map showing
specific trials located throughout the country.

3.  Call us at Project Inform.  Trials conducted at small
community research centers like the Community Research Alliance
in San Francisco or the Community Research Initiative in New York
City may not be listed with the above resources.  If you are
looking for access to a specific drug, we may have information on
who to contact to obtain access.

After locating a desired trial in your area, you can call the
facility conducting the trial and inquire on their procedure for
enrollment.  Enrolling at a research center which conducts HIV
testing is an excellent way to be at the top of their list when
they begin recruiting for new or expanded trials.

What are the Benefits?

The most obvious benefit of participation in a clinical trial is
to get access to a new drug that you might need or want to try.
Other benefits, however, may be more important, especially as
additional ways of getting new drugs become available.  These
other benefits include:

* Getting free medical care.  This is especially attractive to
those who don't have insurance.

* Getting a drug for free.  Thousands of people have gotten their
AZT free by participation in clinical trials.  Many trials
promise to provide free drug for a long period after the trial is
finished.  This benefit will become more important in coming
years if Congress becomes less willing to provide support
programs for expensive new drugs (as many predict it will).

* Getting medical care at the top hospitals and research centers.
This is especially attractive if you can't find a doctor who is
particularly skilled in HIV infection.  Usually, whatever happens
to you while participating in clinical trial is handled by the
research hospital.

* Getting free monitoring.  Good management of HIV infection
requires frequent and extensive lab tests, which can be very
expensive.  Such testing is always a part of clinical trials.  In
some cases, they will try to bill your insurance for the testing,
but they are bound to cover it if your insurance refuses (or if
you don't want your insurance billed).

* Getting medical care or free drug without having it show up on
your insurance records.  Many people are rightly concerned about
possible discrimination when their employers or insurers find out
about HIV.

* A final and very important benefit is the satisfaction of
knowing that your contribution will advance our understanding of
HIV and its treatment.

What are Your Risks?  Your Rights?

At most all drugs, not just HIV experimental drugs, have the
potential for causing harm.  After reviewing the known
information on a drug,we suggest you also receive guidance from
your personal physician or other trusted health professional. As
a general rule, you can assume that the risks are highest in the
earliest phases of research, since less in known about the drug.
Most of the known risks of the drug or the study are listed in a
Consent Agreement you will be asked to sign before entering a
study.  Realize, though, that such consent agreements don't cover
everything and surprises are not uncommon.  For example, the
consent form for the study of suramin in 1986 failed to list the
possibility of damage to the patient's adrenal glands.  Many
people in these studies suffered life-long injuries from this
problem.  In sum, don't fool yourself by believing that a consent
document is all you need to make a decision.

It is often important to conduct a little research of your own
before entering a study.  Ask about the experiences of others who
have participated at a local institutions.  Was the study
ethical?  Did it meet the patient's needs?  Was patient care as
important at scientific discovery?  What happened to people when
the trial was over?  Often, the best sources of information are
people you know.

It's also critical to know what will happen if you experience a
serious problem while on the study.  Usually, the hospital will
take of matters, but there are some exceptions, so it pays to
ask.  While most people are satisfied with the care they receive
in studies, some are not.  We hear a variety of complaints that
differ from one study to the next.  It helps to remember that the
purpose of the studies is not primarily to treat you or make you
well, although that is a hoped for side effect.  The primary
purpose of a study is to learn about a drug.  The more you know
going in, the less likely that you will be surprised or
disappointed by anything that happens.

In the majority of clinical trials studies, all medical records
and lab samples are coded with a number instead of the patient's
name to ensure confidentiality.  You are entitled to all
information on the kind of drug being tested, its previous
testing history results, the possible benefits and harmful
effects it may have, how long is the study, if you will be
hospitalized and for how long, the type of long-term follow up
provided and what other medications can be used while in the
study.  You have the right to withdraw from any study at any time
and for any reason without prejudice.  You cannot be forced to
continue in the study against your will.

What Happens When It's Over?

It is important to ask this question during the initial screening
interview for entry into a clinical trial.  Some pharmaceutical
companies will allow patients to either enter the next phase of
testing, or to research the drug outside the study on a
maintenance therapy basis IF the drug has shown to be harmless
and there is evidence of some degree of effectiveness.  Not all
drug trials have this option.  You have the right to ask for this
information; use it!

Help Us Help Others

If you are on a study, Project Inform would like to hear from
you.  Many results are not released soon after a trials
conclusion.  This delay is often due to the need for researchers
to publish in a medical journal before going public with new
data.  This can take many months.  By keeping us informed of your
experiences, we can keep our callers updated.  Similarly, if you
have problems with the way you are treated either in a study or
applying for one, we may be able to help or refer you to someone
else who can.

Also, small community trials and innovative treatment protocols
are brought to our attention by people like yourself.  Don't
assume we have all the information on all trials in the U. S.,
because we don't Call us or better yet, send us printed
information on any studies you hear of.

*****

Project Inform Fact Sheet

DDI - Dideoxyinosine - (Videx)

Principal author:  Marjorie Little

What Is It?

DDI, (trade name Videx) is a new antiviral drug that appears to
inhibit reproduction of HIV and slow the damage it causes.  One
of the drugs called nucleoside analogues, DDI has many
similarities to AZT.  Like AZT, DDI was originally studied for
AIDS use by the National Cancer Institute.  Both drugs operate by
interfering with the ability of HIV-infected cells to produce new
virus and can cross the blood-brain barrier.  Both are best
called maintenance drugs:  that is, they at best slow progression
of HIV infection, but do not eradicate or eliminate the
infection.

No amount of AZT or DDI will ever be a cure for AIDS.  But they
may be the best current therapies for slowing the activity of the
virus and, at least for a while, retarding the decline of the
immune system.  The principal advantage expected of DDI over AZT
is that it appears to have lesser and different toxicities.
Whether it works as well as, better than, or less well than AZT
is truly not yet known.  For the many people who cannot tolerate
AZT or no longer benefit from it, DDI seems a reasonable choice,
if not the only choice they have.

Background

Bristol-Myers, one of the largest pharmaceutical companies,
successfully bid for a license from the government to develop and
market DDI. Phase I trials began in 1988, even though development
had begun much earlier.  While AZT was undergoing its first
clinical trials, a drug called DDA was under study as a low-
toxicity AZT alternative.  Early research with DDA however,
showed that the body quickly converted DDA to something else -
DDI, which in turn appeared to be active against HIV.  Once it
was clear that DDA was being converted into DDI, researchers
changed tracks and started over again, looking at DDI directly.
Because of this false start, the development of an AZT
alternative has taken much longer than expected.

DDI is now the first AIDS drug ever widely released the basis of
Phase 1 studies (most go through 3 phases, while some, like AZT,
were released after only 2 phases due to emergency
circumstances).  Although Phase I studies are primarily concerned
with toxicity and finding proper dose levels, the early results
reported for DDI were sufficiently encouraging to warrant its
release to broader groups of patients without waiting for
conclusive evidence.  Long-time pressure from AIDS activists,
combined with DDI's apparent effectiveness in reducing p24
antigen levels and providing a modest increase in T4 helper
cells, are the two major factors which made this early release
possible.  The benefits so far noted for the drug, however, have
not occurred for alt patients, but this is typical of other drugs
as well.  Side effects so far appear to be modest.

DDI remains active for around 12 hours after it is ingested (much
longer than AZT, which breaks down in just a few hours). As a
result, the timing and frequency of DDI use are much less
critical than AZT, with doses needed only once or twice a day.
What this means is NO MORE BEEPERS and NO MORE MIDNIGHT PILL
SNACKS!

Government researchers are optimistic about the potential of DDI.
It is a critically needed alternative for those who can not
tolerate AZT, and may be useful for those failing on AZT.
Combination therapy or alternating therapy using both DDI and AZT
may provide the benefits of each drug white minimizing their side
effects and slowing development of drug resistance. Studies might
someday show it to be a better drug overall than AZT if it is
proven as well as less toxic.  But this is by no means certain
today.  It equally possible that it will be less effective
overall than AZT.  For now, the benefits of AZT are far better
proven, so needlessly switching DDI would represent an
unnecessary gamble for anyone presently doing well on AZT.

How Does It Work?

Anti-HIV drugs can so far be classified into three groups:

* agents that interfere with the virus' ability to reproduce,
such as AZT and DDC;

* agents that prevent the virus from linking up with cells in the
body, such as soluble CD4 and peptide T;

* agents that may selectively kill infected cells, such as the
experimental Compound Q.

Researchers agree that DDI fits in the first category.  It
interferes with the virus' reproductive cycle and thus should
prove useful by reducing the amount of new virus produced.

What Does the Research Show?

In vivo studies show that DDI is effective in preventing the
reproduction of HIV but is not toxic to immature cells developing
in bone marrow (a key advantage over AZT).  Based upon these
findings, Bristol-Myers and the National Cancer Institute began
multiple in vivo Phase I studies in July of 1988.  Three groups
participated in giving the drug to a total of 90 volunteers.
Scientists from the National Cancer Institute began the first
study, while researchers affiliated with the University of
Rochester and New York University Medical Center made up the
second group.  The third group worked out of the Boston
University School of Medicine.  At all three centers, subjects
were given increasingly high doses of DDI to determine the
maximum tolerated dose.  Because of this particular study design,
which is based on the way chemotherapy drugs are developed for
cancer, it was inevitable that toxicities would eventually be
found.

In the NCI study, 25 males and 1 female were treated, ten with
AIDS and 16 ARC. All had T4 counts of less than 300.  Results
based upon 42 weeks of therapy indicate that DDI can produce
increases in the T4 count, in the total number of immune cells
and in the T4/T8 cell ratios - in some patients.  The greatest
degree of improvement was seen in subjects in the four highest
dose groups.  People receiving higher doses also showed more than
an 80% decrease in circulating p24 antigen levels.  These also
showed the greatest improvement in immunologic functioning, as
well as increased energy levels.  People at the highest dosage
levels each gained an average of 3.5 pounds.  In a related pilot
study, two diagnosed with AIDS dementia showed improvement in
mental functioning as a result of treatment with DDI.

Although final reports are not yet available from the New York
and Boston studies, preliminary data presented at the Montreal
International Conference on AIDS was also encouraging. Available
data points to increases in T4 counts and decreases in p24
antigen levels for some patients as a result of DDI therapy.  Two
people in the Boston study experienced remission of hairy
leukoplakia, although this may not be significant because of the
small number.

What About Side Effects?

The most common side effects of DDI reported by the NCI
researchers are increased uric acid levels, headaches and
insomnia.  Currently, there has been no evidence of substantial
toxicity in IV doses as high as 3.2mg/kg every 8 hours or oral
doses of twice that.

These preliminary reports indicate that DDI may be less toxic
than AZT, at least in some aspects of its activity.  Anemia, the
most common serious problem with AZT, was not observed, nor was
there evidence of significant white count suppression. Together,
these findings suggest the drug is not toxic to bone marrow.

The most serious DDI toxicities noted have occurred at the
highest dose levels.  In particular, several people receiving
daily doses in excess of 1.75 grams (nearly 3 times the expected
normal dose) suffered painful nerve damage in their feet
(peripheral neuropathy) - a common drug toxicity.  Contrary to
press reports in the New York Times and repeated elsewhere, this
effect was not the cumulative result of long-term DDI use,but
occurred only in response to the high doses.  Neuropathy has not
yet been reported on the normal or lower doses, no matter how
long they have been used.  Some decrease in panacreatic
functioning is also being watched as a potentially dose-limiting
side effect, but this problem was seen only in a small number of
patients.  These toxicities appear to be reversible if detected
early and DDI use discontinued.

The ultimate picture of DDI side effects remains uncertain,
however, and highly dependent upon whom you listen to.  NCI
researchers seem willing to minimize the reports of side effects,
while researchers working with competing drugs suggest the
problems are worse than what is reported.  Several long-term DDI
patients PI has spoken with suggest that there are indeed serious
side effects when the drug is used at higher doses.  A number of
such patients have been taken off the drug permanently.  It would
be foolish to expect that a drug for such a toxic disease as AIDS
would be totally free of side effects. For now, the only major
question is whether DDI's side effects are less than those of
AZT.

What Is Happening Now?

Research protocols:

Bristol-Myers is just beginning large Phase II trials on DDI.
Approximately 2,600 people will be invited to participate on a
nationwide basis.  Initially, three different protocols will be
used.  One will compare the effectiveness and toxicity of DDI and
AZT in people who have taken AZT for 48 weeks or less.  The
second will compare the drug's effectiveness and toxicity in
people who have tolerated AZT therapy for 12 months or longer.
This protocol asks whether switching to DDI might be advantageous
for people who have used AZT for long periods and might now be
experiencing some loss of effectiveness.  The third protocol will
compare the effectiveness and toxicity of three different doses
of DDI in people who can not tolerate AZT therapy at a all.
Participation in these studies will be limited to people with
AIDS or advanced ARC. All will be double blind, but none will use
placebos.  In the first two, volunteers will be randomly assigned
to received either DDI or AZT (they will not be permitted to
chose their favorite).  In the third study, all will receive DDI
but will be randomly assigned to different doses.  The drug will
be administered orally every 12 hours on an empty stomach.  It
will be packaged as a powder that will have to be mixed with
water.  Each packet will also contain an antacid necessary to
neutralize stomach acid which might otherwise destroy the DDI.

Treatment Protocols:

Bristol-Myers anticipates that it will take the two years to
achieve conclusive results, a long time to wait for those who
might need or want the drug but aren't in the studies.  Thus, in
the meantime, the company has agreed to provide DDI free to some
groups of patients under a program worked out with FDA.  The
system is similar to, but not the same as, the parallel track
concept promoted by Dr. Anthony Fauci, director of NIAID.
Bristol-Myers will provide DDI under a Treatment IND (a license
to distribute an experimental drug for treatment purposes)to
people with AIDS or ARC who cannot tolerate AZT and meet certain
other criteria (subject to change) .  Under a separate
compassionate use or open label protocol, they will make it
available to people with AIDS who are failing on AZT.

How to Get DDI

Many who wish to begin DDI therapy will be asked participate in
the research protocols.  It is critical to the future of programs
such as parallel track that enough people quickly sign up for the
three DDI studies.  If this doesn't occur, we will have seen the
last of early use programs for some time to come. The studies
must be the first choice of everyone who is qualified, as they
also provides the greatest additional benefits (such as free
medical care and monitoring).  Those who do not qualify for the
research protocols or cannot participate in them might instead be
served by the Treatment IND protocol or the open label protocol.
The latest information on protocol requirements and locations is
available from the Bristol-Myers Product Information line at 1-
800-662-7999 or the NIAID hotline at 1-800-TRIALS-A.

To be eligible for DDI under the Treatment IND protocol (for
people who are AZT intolerant), you must:

* be ineligible for the research protocols or unable to
participate in them

* be HIV positive, with symptoms, and have a diagnosis of AIDS or
ARC

* be proven intolerant of AZT at a dose level of 500mg.  per day
or less, as defined by any one of the following:
- decrease in hemoglobin level at a rate of at least 2 g.  per
month
- decrease in neutrophil count to less than 750, recurring
after at least one rechallenge with AZT (you must get sick from
AZT twice to prove eligible)
- severe vomiting or nausea without some other cause; this must
occur despite given AZT with food and with stomach-calming
drugs such as Compazine
- severe headaches which don't respond to treatment; recovery
and recurrence must occur on rechallenge with AZT (again, you
must get AZT-sick twice, and you have to get better when you
stop taking AZT)
- acute psychosis or several agitation with recovery and
recurrence on rechallenge
- declining muscle strength associated with elevations of CPK
of greater than 1000, which disappear with discontinuation of
AZT and recur with rechallenge

To be eligible for the open label protocol (for people who are
critically ill and failing on AZT), you must:

* be ineligible for the research protocols or unable to
participate in them

* have a diagnosis of AIDS

* have at least one of the following problems,, despite using
at least 500 mg.  of AZT for 6 or more months:
- involuntary weight loss of 2 to 2.5 lbs per week for 4 weeks
- marked neurological deterioration (dementia causing
significant impairment, psychosis, PML, or transverse myelitis)
- opportunistic infections at least three times in the last six
months
- T4 count less than 50 on two occasions at least one month
apart
- Karnofsky score of 40% or less for at least one month due to
AIDS

In both programs, there are additional exclusions which screen
out the sickest people, as indicated by lab markers.  Apparently
Bristol Meyers doesn't want DDI held accountable for the fate of
the most seriously ill people.  Moreover, once a person is
entered into the program, fairly extensive lab follow-ups and
reports must be made.  Clearly, this will drastically limit the
usefulness of the program for the poor, the uninsured, and those
without a regular physician.

Before being accepted in the Treatment IND or open label
protocols, everyone will first be reviewed for eligibility in the
Phase II trials.  No DDI will be released directly to
participants but will instead be distributed directly to doctors.

Those interested in participating in any of these protocols
should have their doctors contact Bristol-Myers.  Once the
required forms have been completed and forwarded, the company
will provide the doctor with a 30-day supply of DDI for those who
qualify.  At about day 15 of treatment, you will have to see your
doctor again for evaluation and completion of follow-up forms.
Once Bristol-Myers receives these forms, it will provide the next
30-day supply of DDI. Participation in this protocol will require
seeing your doctor monthly to assure continued access to DDI.

If Bristol-Myers can not fulfill their promises, or if the rules
of the program are so harsh that most people who want it cannot
get DDI, the drug will probably become more widely available on
the black market.  Previously, a small supply of good quality DDI
was available from alternative sources at a high cost of around
$600 for a month's supply.  While this is hardly the best way to
distribute a drug, the system often leaves people little choice.

Commentary

Although DDI appears to be less toxic than AZT, little is known
about the effects of long-term use.  All people taking DDI,
regardless of how they obtain the drug, should be closely
monitored by a physician.  No information is yet available on how
DDI may interact with other drugs in common use such as
acyclovir, DHPG, alpha interferon, or any of the products
available through the buyers clubs.

Overall, access to the drug through the Treatment IND and open
label programs represents an improvement over previous, even more
restrictive approaches, but it is hardly the compassionate
breakthrough that Bristol-Meyers and the government claim.  The
criteria for qualifying for the treatment programs is
unacceptably harsh and demanding.  Most importantly, it is
dependent upon having an aggressive, well informed physician who
is willing to do extra paper work,and upon the ability of the
patient to have extra lab work done.  Taken together, the
weakness of these programs make a potent case for why the
parallel track program described by Dr. Fauci and AIDS activists
is still so critically needed, even for DDI. While activists are
currently working to correct the current problems with DDI
access, there is no guaranty of the outcome.  Calling such a
program "an improvement" is sad testimony to how bad things have
been previously.

Yet,it would still be a mistake for everyone with HIV to jump on
the bandwagon and demand DDI. There is no evidence that it will
help more than AZT, and some suggestion that it will not do as
well.  Once we get over the excitement of having a new
alternative in reach, hard choices must be faced.  Hopefully,
they can be faced rationally and not from the center of a blind
stampede.  Nonetheless, we firmly believe that people with life-
threatening illness are entitled to make these choices for
themselves.  In the long run, they are far more concerned with
their health than a barrel full of bureaucrats.

Several crucial concerns remain:

1.  How many people will receive DDI while the trial are going on
?  The company has indicated they expect to have 5,000 to 10,000
people on DDI by the end of 1989.  It has been estimated that
within the next six months,25,000 to 30,000 people win become
intolerant to AZT.  win Bristol Myers respond to an of them as
promised?

2.  What effect will DDI distribution have on the future of drug
trials and the development of other new treatments ?  Other
pharmaceutical companies may have difficulty attracting
volunteers for their studies if everyone with AIDS or advanced
ARC has free access to DDI (at least if it is working well).  On
the other hand, why should anyone be denied the use of a good
drug just so a drug company will have someone left to test
another new drug on?

3.  Will DDI tolerance become a problem?  There is every reason
to expect that it will, so why not begin thinking about
alternating therapies from the beginning?

4.  Will DDI have the same prophylactic benefits for HIV
positive, asymptomatic people as AZT does?  We would expect this
to be the case, but there is no research currently underway to
answer this critical question.  Will we have to wait years for a
such a program to start?

5.  Will DDI provide any therapeutic benefits for people whose
disease has clearly progressed  to end-stage ?  Whether it does
or not, on what basis should government be permitted to deny them
a last chance?

6.  If and when DDI is approved by the FDA, what will it cost?
Will Bristol-Myers have total control in setting the price?

Perhaps now is time to begin thinking about these questions,
instead of waiting until years later as was done with AZT.

*****

DDI at a Glance

Pro:
- Strong early signs of effectiveness
- Evidence of lesser/different toxicities than AZT
- Studied in 90 people in multi-center Phase 1 trial
- Easy to we, less demanding on patients
- May be useful when AZT wears off
- May someday be used in combinations or alternation

Con:
- AU data is preliminary, needs confirmation
- Evidence of neuropathy at very high doses
- At best, unlikely to be any more effective than AZT
- Activity is limited to slowing spread of the virus
- Treatment IND and open-label programs are overly
restrictive, unfair to AZT failures
- Access through clinical trials requires randomization
between AZT and DDI (you don't get to choose)

Buying/Access:
- First line of access is through clinical trials
- Access for AZT-intolerant through Treatment IND
- AZT-resistant may be served by open-label program
- True "parallel track" is yet to come
- Underground sources are very limited and costly

*****

PI Perspective...

* Distributes information on a limited number of well-qualified
treatment options;

* Advises on access to treatment;

* Encourages personal empowerment through active treatment
strategies;

* Increases awareness of the obstacles which heed progress in
research.

How often does it come out?

* About 3 times per years, or whenever we can afford it Pl is
funded primarily by donations.

Do I pay for a subscription?

* It is free.

What does a donation pay for?

* A toll-free treatment hotline, the journal, outreach on early
diagnosis and treatment strategies, and efforts to enable sane
research and treatment access policies.

*****

==============================================================

In memory...

We dedicate this issue of PI Perspective to Dennis Hathaway,
Robert Parr, Ron Fisher, Richard Livingstone, Steve Whittaker,
Scott Schaefer, and all the others this year for whom the system
didn't move fast enough or try hard enough.

Their memory lives on in the work that remains.

==============================================================

*****

For your information

The last Pl Perspective highlighted the benefits of an individual
mail order pharmacy.  It is is equally important to be aware of
the advantages and benefits provided by local pharmacies.  These
include:

* personalized, immediate service
* counselling regarding drug and food interactions, managing
side effects, and the latest data on new treatments and dosage
* immediate, local response to your questions and concerns
* collaboration between your doctor and your pharmacist
* ability to work out payment plans
* referrals to local support agencies and consumer bureaus
* information about alternate resources and programs
* knowing and caring about you as a who/e person
* in some instances, acceptance of insurance as payment in full

Whatever pharmacy you choose, it will be a critical partner in
our health care.  Choose wisely and seek to meet the broadest
spectrum of your needs.

(Thanks to the Valley Medical Pharmacy, Sherman Oaks, CA for
these valuable tips)

*****

Project Inform:

The Basic Message
* Learn your options and line up your support.
* Get tested, anonymously.
* If positive, consider anti-viral treatment (and get a full
immune health workup).
* Monitor T4 cells quarterly, charting the trend.
* If the trend of T4 cells is downward or falls consistently
below 500, consider both anti-viral and immune boosting
therapy.
* If the trend of T4 cells falls below 200, use prophylactic
(preventive) treatment against pneumocystis (aerosol
pentamidine, if possible).

*****

Organizational Update

Town Meetings:  The fall and winter schedule for Project Inform
town meetings in the Bay Area is listed below.  The meetings will
be held at 7:30 p.m. at the MCC Community Church, 150 Eureka
(between 18th and l9th on Eureka), in San Francisco. Note that
there will be no meeting on December 27th.

Project Inform Town Meeting Schedule

First- Timers   Regulars
4          October           25
1          November          29
6          December      No meeting
3        January 1990        31


San Francisco AlDS DANCE-A-THON:  Project Inform is a beneficiary
of this year's 5-hour DANCE-A-THON. This all-fun benefit will be
held on December 3, 2 - 7PM at your choice of three popular Bay
Area Clubs:  the I-Beam (1748 Haight), the Kennel Club/Box (628
Divisidero), or the Club Townsend (177 Townsend).  Participation
simply requires a willingness to secure pledges (from friends,
relatives, and co-workers) and a desire to dance 'til you drop.
Call 415-863-4679 or the PI office for registration forms.

Holiday office and hotline schedule:  The Project Inform office
and hotline will be closed Thanksgiving Thurday and Friday,
November 23 and 24,1989.  The office and hotline will be closed
Christmas day, Monday December25,1989, and New Year's day,
January 1,1990.  The office and hotline will operate on a reduced
schedule and with a reduced staff for the week between Christmas
and New Year's, December 26 through 29.  Hours for those days
will be from 10 a.m.  until 2 p.m. Pacific Time.

Bartender's Bash benefit for PI:  Bench and Bar, located at 120
11th Street in Oakland, is hosting a benefit for Project Inform
on Tuesday, November 7.  Prizes will be raffled off, and the bar
will feature specials throughout the evening.  All bartenders and
their friends are encouraged to attend.  A $2.00 donation is
requested.  For more information, call 444-2266.

PI T-shirts for sale! Be the first on your block to wear a
Project Inform T-shirt.  Tastefully au currant with a southwest
motif and a logo saying "It's never too early to take charge of
your health," they are Santa Fe green and Taos red on white.
Prices are $12 at the PI office or $14 by mail.  Mail orders,
send check or money order to the PI mailing address below, and
mark the envelope tshirts!

Wish List! The foollowing are just a few of the items needed at
the PI office.  Can you help?

carpeting, electric typewriters, cubicles, color television,
conference table chairs, lamps, locking file cabinets, step
ladder, couch and end table group, room dividers, VHS VCR, IBM AT
compatible computers

If you can donate any of these items, give us a call at (415)
5S8-8669.

Your Help Make a Big Difference

Please make a contribution, bequest, or give a gift in someone's
name.  Ail donations are tax deductible.  Use this I coupon:
your name is on the other side, so there's no need to sign it.


$25   $50   $75  $100   $250    $500  $1000

Or use the service for yourself or a friend.

PROJECT INFORM
347 Dolores, Suite 301
San Francisco, CA 94110
National - 800-822-7422
Califoria - 800-334-7422
Local  --  415-558-9O51

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