ddodell@stjhmc.fidonet.org (David Dodell) (07/23/90)
AIDS TREATMENT NEWS Issue # 106, July 6, 1990
Conference Report, Part I
Sixth International Conference Overview from Marcus Conant, M. D.
Announcements:
Parallel Track Letters Due;
ACT UP Publishes AIDS Research Agenda;
AIDS in Prison Conference;
California Budget Cuts;
Women and Clinical Drug Trials;
Conference Abstracts Available
CONFERENCE REPORT, PART I
The headline story from the Sixth International Conference
on AIDS is that (as expected) no "blockbuster" advances were
announced. But behind the headline, this Conference produced
much useful information -- more than any previous meeting. Few
reporters, scientists, or physicians can look through all the
information presented; therefore many potentially useful
developments may be lost, and never be reported in the general
press or even in scientific journals.
During the Conference we focused mainly on examining and
photographing poster presentations, and talking with people we
met in the poster aisles. Many important oral sessions had
scheduling conflicts with other meetings, so we bought audio
tapes. The most convenient single information source remains the
Conference abstracts, about three thousand of them published in a
three-volume set. Although the abstracts could not be changed
after January, the "bottom line" results reported seldom changed
between then and June, so the abstracts remain useful. They are
generally well organized into topics, easier to read than in
previous years, and have subject and author indexes.
We plan to examine thoroughly two of the four tracks of the
Conference -- Basic Science (Track A), and Clinical Science and
Trials (Track B) -- seeking reports we believe could be useful to
our readers. We will cover the other two tracks, Epidemiology
and Prevention (Track C), and Social Science and Policy (Track
D), only sporadically. We are now looking through the voluminous
Tracks A and B information to pick out potentially useful items,
and group them by specific opportunistic infection, particular
HIV treatment, or under other practical headings. We expect our
next few issues to be largely devoted to this Conference, but we
cannot be sure, since issues of AIDS TREATMENT NEWS are not
planned in advance but cover whatever seems most important at the
time.
We are also following political developments concerning the
Conference. Some of them raise issues about the fundamental
contract between government and the governed. We have chosen to
wait to see what develops on these matters, and to focus on
scientific and medical information for now.
For this issue we are lucky to have the report from Dr.
Marcus Conant, below, on some of the major Conference
developments as seen by one of the country's leading HIV
physicians.
SIXTH INTERNATIONAL CONFERENCE OVERVIEW FROM MARCUS CONANT, M. D.
Marcus Conant, M. D., is in private practice in San
Francisco, where he has one of the largest HIV practices in the
United States. He has treated AIDS since it was first
discovered, and has conducted clinical trials of experimental
treatments and published over 30 papers on AIDS and HIV since
1983. Immediately after the Sixth International Conference on
AIDS in San Francisco (June 20-24), Dr. Conant met informally
with other leading physicians to review the information reported,
and to seek consensus on how it should affect their practices.
On July 2 Dr. Conant called a two-hour public meeting in San
Francisco to tell his patients and others about results of the
Conference and the physicians' review session afterwards. The
following is from our notes of the July 2 meeting. We thank Dr.
Conant for permission to use this material, and for reviewing it
for accuracy.
History of the Annual International Conference on AIDS
Each year's International Conference has had its own theme.
"The first Conference in Atlanta, in 1985, was clearly a
meeting with a lot of hope; everybody went there saying, finally
it's coming together, finally after five years of the epidemic
we're going to see some movement. The next year in Paris was
clearly the meeting of despair. People were expecting some real
breakthroughs, and there weren't any; everyone came away
depressed.
"The third year in Washington (June 1987) AIDS came of age
scientifically; that was the first international meeting where
the heavy hitters moved into the field -- people from immunology
and virology, specialists in other viral diseases, people who had
made vaccines. With those heavy hitters came their young turks
who want to get Nobel prizes, because if you're really bright in
science you hang around with somebody who's really bright. AIDS
also came of age politically, as the White House recognized AIDS
as important enough to send George Bush, then Vice President, to
address the meeting; Bush's speech was booed by the audience.
"The next year in Stockholm (1988) was a period of
confirmation. The studies on AZT were being done, and everybody
was finding the same result, in Africa, Europe, or the United
States. Last year in Montreal, one of the major themes was women
and children and AIDS.
"Before this year's Conference in San Francisco, some of us
had despaired of having more international meetings. There was
so much concern about turmoil that many were saying that there
may be no place for an international AIDS meeting, each specialty
will have its own. To the great credit of Paul Volberding and
John Ziegler, they organized a meeting that did bring it together
for everybody. They assured that for the next few years we will
continue to have international AIDS meetings. I think
unfortunately that the behavior of the United States government
will assure that those meetings will not occur in this country."
AZT
No big surprises about AZT came from the Conference, but Dr.
Conant mentioned some significant results:
* We did not hear of any new toxicities.
* We are seeing much less myopathy, probably because of the
lower dose. "More people are seeing what we had observed, that
if you are on high-dose AZT, 1200 mg per day, and are exercising
a lot, that may trigger the myopathy, and if you stop working out
for a while and reduce your AZT, you may then go back to work out
moderately and see your CPK (creatine phosphokinase level) stay
down and not rise."
* We are seeing no liver toxicity on the lower dose. "So if
you are on AZT and your liver enzymes start going up, and your
doctor thinks it is due to the AZT, tell him or her that we need
to look further. Could there be something else that's causing
liver toxicity?"
A questioner asked how long people have been followed on the
lower dose (500 or 600 mg per day). Dr. Conant answered that
people have been on this dose and followed for a little over two
years. Some people have been on the high dose for about five
years.
* Only about one percent of patients with over 250 T-helper
cells need to stop AZT because of toxicity, when using the low
dose. That compares with up to 40 percent in the early trials,
for people who had had pneumocystis and took the high 1200 mg
dose.
* The lower the CD4 (T-helper cell) count when patients
start AZT, the less likely they will be to lower p24 levels (a
measure of viral activity in some patients). "Clinicians need to
hear this. If you start AZT at 200, you have less chance to lower
the p24 than if you start at 400 or 500."
* AZT is working about the same in children as in adults,
and the same in women as in men.
* A very small study has shown AZT to be effective at 300 mg
per day. "I would keep that figure in the back of my mind. If
you have to do dose reductions, and you want to know how low to
go, I would try not to go below 300 mg per day; that's for a 150
lb man or woman."
* European data has shown that AZT does not need to be given
every four hours. "So (at the physicians' meeting after the
Conference) we largely agreed that we would be recommending 200
mg three times a day."
* What about viral resistance? "We spent three hours
talking about that, and the bottom line is we don't know at this
time. The consensus was that resistance is a concern, but at this
point there is more compelling data that people with below 500 T-
helper cells do better with AZT than without it.
"Also, we don't know if people who develop resistant virus
are therefore going to get sick; does that really constitute drug
failure? For example, if ddI became available tomorrow by
prescription, and you had been on AZT for two years, and I found
you had resistant virus, and you tolerated the AZT well, would I
stop the AZT and put you on DDI, or would I reduce the AZT to 300
to 500 a day and put you on ddI in addition to the AZT? Does
resistance mean that the drug has totally failed, or only that we
might want to add another antiviral? We are far from any
definitive answer.
"Will resistant virus be transmitted? If so, treating
persons who caught the virus could be a more difficult problem."
ddI
Question from the audience about the risks and benefits of
ddI: "Some two percent of patients on the drug for seven months
have experienced pancreatitis. The high dose is associated with
pancreatitis; low doses do not appear to be. Pancreatitis is
much more common in persons with a prior history of pancreatitis,
or of liver disease. If someone has chronic active hepatitis, or
elevated liver enzymes, the physician will probably want to watch
even more closely.
"Hemorrhagic pancreatitis with death has been seen. There
have also been deaths, probably due to arrhythmias (heart-rhythym
abnormalities), in people simultaneously taking rifabutin,
clofazimine, and ddI.
"Triglycerides may be elevated prior to elevated pancreatic
enzymes (amylase).
"On the positive side, T-helper cells rose about 30 percent
in a group of people on ddI. Physicians are seeing p24 reduction,
and viral culture going negative, but nothing more dramatic than
with either AZT or ddC.
"ddI appears to be working in children.
"The ddI dose they're using is around 250 mg twice a day for
a 70-kilo man, 375 for heavier people. (Note: we reported in
the May 18 issue of AIDS TREATMENT NEWS that some patients in the
open-label study -- the expanded-access program -- have reduced
their dose by taking only one of the two daily doses --
preferably with the knowledge of their physician and Bristol-
Myers.)
"Concerning the rise of T-helper cells, there has been a
statistical problem in some studies. To take an illustrative
example, suppose everyone in a study stays the same, except for
some of the people with the lowest T-helper counts, who have big
declines in the count and therefore decide to drop out of the
study. Then the overall average would go up -- even though not a
single patient went up -- just because those at the lower end
dropped out. Studies can be adjusted for this particular bias by
taking each patient's baseline T-helper count as that person's
starting point, and averaging the changes, plus or minus. But
simply reporting the average or median T-helper cells in the
group before treatment, and in the group after treatment when
some patients have dropped out, can be misleading.
"One of the criticisms of the ddI open-label study is that
those for whom the drug doesn't work drop out."
ddC
"ddC looks more promising than it did last year. T-helper
counts are up. A lower dose of ddC has lower toxicity, and the
toxicity is predictable. There have been no fatalities from ddC.
"ddC is probably safer than ddI. I think if you polled half
a dozen experts now and asked if you had to go off AZT, what
would be the next drug you would choose, ddC would be the choice.
Unfortunately, access will be limited for a time.
"The best ddC data yet is in the paper Gottlieb presented to
the Montreal AIDS conference last year."
Antiviral Combinations
A member of the audience asked whether to add ddI to AZT, if
ddI were available. "I don't have an answer. But if I had been
on AZT for a year and a half, and had evidence of disease
progression, and I could take both drugs, I would consider doing
so. There's a place for combination therapy.
"I liked having the AIDS activists in the Conference;
sometimes they raised the most cutting questions. On
combinations, the traditional way is to test drug A, get to know
everything about it, then test drug B, and only later try
combining the two. But since everybody seems to agree that
combinations is the way to go -- they've been talking about it
for years now -- activists asked why not go ahead and do it? The
answer was, 'That's not the way we do it.' The question was
useful, because if you watched the speaker who was answering it,
you could see written all over his face the thought, 'Isn't this
stupid?' That may be the first time the thought occurred to him
-- having to say it publicly -- that maybe we ought to move on."
Question: is there any data based on previous experience with
other diseases as to how the drugs should be combined?
"The answer unfortunately is no. These are synthetic
nucleoside analogs, and except for acyclovir to treat herpes,
there is not yet another model; it is not the same as
chemotherapy.
"It's not as bleak as it sounds. We think that much of this
data now will come from animal models, and that we won't have to
wait to do the whole thing.
"There are some experiments on combining drugs, for example
the ddC study at Stanford which is testing alternations of this
drug with AZT."
Surrogate Markers
"What about p24 or virus in the blood as a surrogate marker?
The answer at this time seems to be that they are not reliable
enough to use for clinical management. About 20 percent of
patients who have negative p24 still die of AIDS.
"Even the Ho quantitative viral assay is not sensitive
enough that we can say that you should stop AZT at this point and
go to ddI.
"We're hearing that p24 and viral-culture tests are useful
markers, and can be used by the clinician from time to time, but
you would not stop a study based on those. I asked at the
meeting -- with Volberding, Fischl, Schooley, and others -- is
there a surrogate marker other than disease progression or death
that you would choose to use to stop a study? Their answer is
still no. That is the science at this time, unfortunately."
Soluble CD4
"Bad news. It has no toxicity, but it does not cross the
blood- brain barrier. But the worst news was reported by David
Ho. He tested soluble CD4 with virus grown in the test tube, and
it was very effective in removing virus. He then took native
virus from patients, and the CD4 didn't work. Smart people are
still researching CD4; they are not giving up. But these results
are not what we wanted to hear."
Compound Q
"If you ask, 'Does compound Q work?' I don't know.
'Should I do it?' That would depend on many other variables.
There's not enough data to say. There has been frightening
toxicity with coma in some cases.
"Some of the compound Q results which have been discussed
were not presented at the Conference. We need to ask the hard
questions. If the researchers say the T-helper counts are going
up, we need to ask how they figured that." (See note on
statistical problems with T-cell group means, above.)
"Clearly we need a lot more information."
Peptide T
"There is little good data with peptide T alone. But in one
study, with AZT and peptide T given nasally, it improved
cognitive function compared to AZT alone. If confirmed, that's
very promising. Unfortunately, Dr. Candace Pert is having
trouble now finding funding for her peptide T studies, so whether
we see more peptide T research soon will depend on funding."
Isoprinosine
"A recent article in the New England Journal of Medicine
(June 21) showed that 17 patients on placebo progressed as
opposed to two on isoprinosine. I think you will see more
isoprinosine studies. Clearly this data looks very good; it
looks like hard data. There is a question that it may be blocking
the pneumocystis, not treating the HIV.
"Mark Illeman and I did some of the early isoprinosine
studies back in 1983. One study, which we never could get the
company to fund again, was fascinating. We had 20 men taking
isoprinosine or placebo, and then we would measure how much CMV
(cytomegalovirus) there was in the semen. There was a four-log
drop (10,000 times) in CMV in the people on isoprinosine.
"The trouble was that when the data was analyzed, we had ten
patients on placebo, and their baseline CMV concentrations ranged
from low to high; we had four on drug, and all of them started
low. The company had all the data, and they just told us that
this is all they had to analyze. We didn't know why the other
six had not been included. Without being able to break the code
myself and be sure that we had a good comparison, I was unwilling
to publish the results until we could repeat the study to be
sure. We never could get the funding to do it again."
(Note: Isoprinosine is approved in dozens of countries but
not in the U. S., and is used for treating herpes simplex and
some other viral diseases. A literature search found no
published report of any test of isoprinosine and CMV -- meaning
that if the drug is useful in suppressing or treating this
infection, we would not know it.)
Oral Interferon
"Sublingual alpha interferon? Nobody knows. The consensus
of our small meeting was that if it does work, it's without
rationale; we don't understand how it could work. People are
waiting for more data."
Hyperthermia
"Dr. Alonso was here, and presented some of his data. I met
later with an internationally recognized immunologist who had met
with Dr. Alonso. We all want that to work; it's easy to do. But
the immunologist was concerned that Alonso's team had not brought
with them all the data they were claiming. For example, they
claimed that scans had shown that KS in the lung had improved --
but they didn't bring the scans to San Francisco. The
immunologist offered at his own expense to fly to Georgia and
look at the data; we don't know what will happen with that.
"It's so sad, because something like that comes and you've
got lots of desperate people who want answers, including the
doctors ...
"The claim is that they're heating the blood higher than
107-108 degrees outside the body. We've seen lots of patients
with a temperature of 107 for a few hours, and it didn't cure
their AIDS.
"I'm also concerned that Dr. Alonso is already saying that
he can determine who will get better after this therapy and who
will not."
GM-CSF
"The data looks very promising; access to the drug is still
limited."
AZT/Interferon Combination
"There is much enthusiasm for using very low doses of alpha
interferon, such as a million units a day, or three million units
three times a week, for people with high T-helper counts, 300 to
500, to see if this can prevent disease progression."
Acyclovir
"I had thought we had seen the end of the AZT combined with
high-dose acyclovir treatment. But Dr. David Cooper from
Australia, a leading AIDS expert, is still reporting better
survival in 60 patients, with CD4 counts around 30, if they are
on very high dose of acyclovir, 800 mg four times a day. It does
not seem to be CMV-related, but does appear to stop progression
of other OIs."
Question about Conant's use of acyclovir:
"Everybody who had herpes, I'll give 400 mg twice a day --
that's easy and safe, and won't bankrupt you. Earlier, based on
Dr. Cooper's previous reports of less CMV, we were putting people
on high-dose acyclovir, but we didn't see that much difference.
"About four years ago there was a laboratory study
suggesting that acyclovir potentiated AZT. The hope was that
low-dose acyclovir would make the AZT work better. But later
laboratory studies showed that not to be true. So we have been
less enthusiastic about recommending the high doses to people
with less than 100 T-helper cells.
"But at the Conference, the data was from a good
investigator, with good controls, and 60 patients; the ones on
acyclovir are surviving better than the ones not."
Question about long-term side effects of acyclovir:
"We are not seeing any. The biggest concern on the high
dose would be kidney toxicity, and as long as you remain
hydrated, that's not a major concern. You would not want to take
that much acyclovir and hike out of Grand Canyon, however. We
didn't see any toxicity when we were giving the high-dose
acyclovir."
Passive Immunotherapy
"Keep in touch; hopefully a study will be starting soon."
Pneumocystis Prophylaxis
"Out of this Conference came almost irrefutable data that
trimethoprim sulfamethoxazole (brand names Septra, or Bactrim) is
as effective as aerosolized pentamidine in preventing
pneumocystis. It was given as one double-strength tablet per day
-- or given three times a week. Cooper in Australia gives it on
two days each week, one twice on Monday and one twice on
Thursday, and has never had a pneumocystis breakthrough. We will
probably recommend that patients with more than 100 T-helper
cells consider going on one double- strength Septra a day as your
basic prophylaxis for pneumocystis. Then if you get below 100
T-helper cells and want to do aerosol pentamidine in addition to
that, you're welcome to do it, although we're not sure it's going
to help that much more. But the good news is you can trade a
pill that costs about $30 a month for the cost of over $300 a
month for aerosolized pentamidine.
"There were no dissenting votes in the small group of people
we assembled, from here and Australia and Europe. The developing
consensus is that somewhere below 500 T-helper cells you go on
AZT, somewhere below 250 T-helper cells you go on one Septra a
day, and if it continues to fall down below 100 T- helper cells a
day you may want to go on aerosolized pentamidine also.
"There are other advantages of Septra over aerosolized
pentamidine, besides the cost. Pneumocystis is not just a lung
disease, it can be a systemic disease as well. With Septra, you
are prophylaxing systemically, not just in the lung.
"Also, there is emerging evidence that with Septra you are
also prophylaxing against toxoplasmosis, and shigella (a kind of
food poisoning, which also occurs from handling reptiles).
"The bad news is that 20 percent of the people are going to
get a drug eruption (a rash caused by the drug). You may be able
to treat through the drug eruption, by lowering the dose greatly
and coming back up, or you may have to stop the Septra and go to
aerosolized pentamidine."
(Dr. Conant said that if he had to guess, once a day might
be less likely to cause side effects than twice a week, because
it would be easier to build tolerance with the drug every day.)
Question about dapsone for pneumocystis prophylaxis:
"We don't know, there isn't enough data yet. If you are on
dapsone, it's probably reasonable to stay there."
Question: if on pneumocystis prophylaxis and T-helper cells
went over 300, OK to stop?
"Yes, but you might wait for the next T-cell test in four
months to make sure the result was not an aberration."
Question: is there a problem of losing the use of Septra if a
reaction develops (in case one gets pneumocystis in the future)?
"Yes, this is a concern. We are trying to design a study to
attempt to desensitize people to Septra, the same way as you can
desensitize people to penicillin."
Question: if someone has a T-helper count of about 25 and cannot
stop aerosol pentamidine because he's in a study, should he
consider Septra also? He cannot take dapsone because of the
rules of the study.
"Aside from the issue of damaging the study, we have been
telling people for about a year that if they have under 100 T-
helper cells they should consider dapsone in addition to aerosol
pentamidine, to protect against systemic pneumocystis. But if a
study does not allow dapsone, it is unlikely to allow Septra,
either.
"When the standard of care changes, the studies have to
change. They cannot do things to you that are below the standard
of care. So next time you're in, mention hearing experts from
the Conference saying that the standard of care may be changing
to include Septra for people at risk for pneumocystis; ask what's
their reaction to this."
Question: any information about long-term side effects of
aerosol pentamidine?
"Yes. Diabetes has been seen in some cases with long-term
use. The drug may contribute to pancreatitis in patients on ddI.
However, there have been no drug eruptions (rashes). Also, no
loss of elasticity of the lung has been reported."
In response to a question about dapsone vs. Septra for
prophylaxis, Dr. Conant said he guessed they would prove about
equally effective. (The reason the physicians' meeting chose
Septra is that there is more data on it than on dapsone at this
time.) Some dapsone data was presented last year at the
International AIDS Conference in Montreal. Side effects about
the same; Dr. Conant thinks the number of drug eruptions will
probably be less with dapsone.
Treatment of Pneumocystis
"There is now a growing consensus that corticosteroids do
play a role. It looks like cortisone is safe if done properly
and judiciously -- high-dose cortisone, then tapered gradually."
Dr. Poscher, on Conant's staff, explained that "This is used
in severe pneumocystis -- not mild cases -- when patients present
to the hospital requiring oxygen or ventilators. They should be
started on steroids early, within the first 24 to 36 hours of
their hospital admission. In the past the tendency was to
salvage them with steroids three or four days after they did not
respond to treatment. That's been shown not to work at all. It
is the early use of steroids that causes 50 percent reduction in
mortality from pneumocystis."
Toxoplasmosis
Dr. Conant reported that toxoplasmosis is much more common
in Europe than in the United States; the best guess for the
reason why is raw meat in European diets.
Some physicians are trying prophylaxis with dapsone, or
Septra. Dr. Conant said that if he had less than 100 T-helper
cells, he would be on one of these.
There is some enthusiasm for clindamycin for therapy instead
of sulfadiazine.
Tuberculosis
"Tuberculosis is frightening. We are seeing a lot of it
among HIV-positive people in some areas: for example in Miami,
among Asians here in San Francisco, and in Africa. Up to a third
of those cases disseminate, instead of only infecting the lung."
Dr. Conant heard that Dr. Margaret Fischl has 51 cases in
the Miami area, some in gay men, that are resistant to the
standard four-drug combination. This is worrisome, especially
because tuberculosis can spread easily.
Question: if a friend has TB, is on medication for it, is it not
safe to assume he is not infectious?
"Correct. If you have a friend who's just coughing -- I
wouldn't kiss people with coughs, until we learn more about this.
"Every HIV-positive person should have a TB skin test; the
earlier the better. It tells you whether your body has ever seen
TB before; it doesn't mean you're infectious. But the TB you had
(and controlled) could become reactivated, so your doctor would
watch your chest film more carefully. If the test was negative,
you should probably repeat it every year. It's another reason
for having a routine chest X-ray.
"If your immune system is already suppressed, the skin test
might read negative even if it should be positive. The way to
find out is to do a skin test with other antigens; if you react
to them, then you probably would react to TB if you had been
exposed to it" -- meaning that the TB test would be accurate.
(Note: previous reports of TB treatment, before the
occurrence of the drug-resistant strain, had shown that standard
treatment worked about as well for HIV-positive persons as for
anyone else.)
"AIDS presents very differently in different geographic
areas. For example, TB has not been a problem in the gay
community in San Francisco -- but there has been a lot of it in
Miami, and there is no reason it could not spread to immune-
suppressed people elsewhere."
Another geographic example: "In an AIDS ward in Memphis,
many patients have histoplasmosis. But in our practice in San
Francisco we have seen only one case."
Mycobacterium Avium Complex (MAC; also called MAI)
"Dr. Harold Kessler and others presented some beautiful work
(see poster #Th.B. 517) showing that 5-drug therapy with Amikacin
gives the best response in the treatment of MAI. Clearly the
position some were taking two years ago that it is not useful to
treat MAI is wrong; patients live longer and their quality of
life is better if you aggressively treat MAI. The consensus is
becoming that if the disease is diagnosed, treat it aggressively.
"What about using the PCR test to diagnose MAI in two hours
-- instead of six weeks for culture? The problem so far is that
this test may be too sensitive, and diagnose MAI in everybody."
Question about clarithromycin for treating MAI. Dr. Conant is
aware of work in France, but no paper was presented at the
Conference.
Cryptococcal Meningitis
"Fluconazole does not seem as effective as amphotericin
(AmB) for initial treatment. Don't use both, because the drugs
compete. After initial treatment, fluconazole is clearly best for
maintenance.
"The jury is still out on whether to prophylax with
fluconazole -- using one fluconazole a day for persons with very
low T-helper cells -- to avoid the possibility of getting the
disease. There is no data to show whether this is beneficial.
It could possibly be harmful, because there could be unknown
interactions with other drugs the patient was using."
Cryptosporidiosis
"Cryptosporidiosis is becoming less frequent; we do not know
why. Data was presented on diclazuril (poster #Th.B. 520 and
talk by Dr. Rosemary Soave) as a possible treatment."
Syphilis
"Standard blood tests do seem to be effective to detect
syphilis, despite immune deficiency. There are only a few cases
where the tests have been known to fail."
CMV: Oral Ganciclovir
"Oral ganciclovir is not as promising as had been hoped, as
it has poor bioavailability. No benefit was found for CMV
colitis."
Lymphoma
"We are seeing much more lymphoma. A third of those cases
are apparently caused by Epstein-Barr virus. The lymphomas seem
to be coming from chronic infection with some agent -- maybe
Epstein-Barr, or other viruses which have not been identified --
which immortalize the B-cells (making them cancerous) or T-cells.
One speculation -- could it be that Dr. Cooper's patients in
Australia are doing better with high-dose acyclovir because it is
suppressing viruses which cause lymphoma? There is no data for
this yet, it is just a possible hypothesis.
"People who have had KS and survived for many years have
very high levels of IL6. The concern is that large amounts of
IL6 might trigger B-cell lymphomas. So people who have had KS
for several years, who develop a new node that's not been there
before, should talk to their doctor about whether it could be a
lymphoma. We don't know for sure yet about the risk factors, but
this is one to consider."
Other Cancer
"Basal-cell carcinomas are becoming more common --
especially body basal cells as opposed to facial basal cells.
Basal cells very seldom metastasize, so these cancers are usually
not very serious.
"But there has also been much squamous-cell carcinoma in the
anal-genital area, especially in people who had perianal warts.
If you had warts in the anal area and get a bump there that's
growing, get your doctor to make sure it's not a malignancy. If
early diagnosed, it can be excised and is no problem. If you
ignore it for several months months, this cancer may metastasize
and be serious.
"We may see more liver cancer in HIV-positive men --
especially with chronic active hepatitis and alcohol."
Vaccines
"There is much optimism now about vaccines, both for
treatment for those already infected, and for the uninfected.
Much new information is becoming available.
"Dr. Jay Levy reported one case of a chimpanzee which has
now cleared an HIV infection and is antibody negative.
"Other researchers found that women with antibodies to the
V3 loop of the virus do not infect their babies. These
antibodies must therefore be protective. If so, they could be
made either in humans or synthetically and given to patients.
"Salk has been testing his vaccine in persons with HIV for
three years now. Passive immunotherapy is another approach to
providing protective antibodies.
"Murray Gardner presented a magnificent paper on SIV in
primates. Jay Berzofsky showed how you can take the part of the
virus you want to make antibody to, put augmenters on it, and
make even higher antibody levels. But some epitopes of the virus
can facilitate viral replication. So you must design a vaccine
that has the parts you want, with augmenters that make it
multiply, and eliminate the parts that facilitate viral
replication.
"Phil Berman a week before the Conference announced that he
had protected two out of two chimps with a genetically engineered
vaccine."
Dr. Conant attended a Genentech cocktail party and found the
leading vaccine experts there, and much enthusiasm for making a
vaccine.
Epidemiology, Partner Notification, Health-Care Workers
"Belgium has started a partner notification program, and is
finding it very useful in picking up asymptomatic infected
individuals. I think you'll see more discussion of partner
notification in this country in the next year or two. One of the
problems that plagues the government is that, with the gay
community, they can treat the entire community as a cohort, and
say that if you've ever had sex with another man, you are at
risk. But with the heterosexual community, do you test every
heterosexual in America, or do you try to target those
heterosexuals who are at risk? Clearly the latter is the most
cost effective. It may not be the best way to do it, but if you
were managing a government program, you would ask how to target
the people at highest risk. One way to do that would be by
partner notification. That has not been widely done, for civil
liberties reasons. I think you will be seeing it discussed more.
"There is much concern about occupational risks to health-
care workers. At least two have become HIV positive after a
serious needlestick injury, despite high dose AZT given
immediately. We had hoped that AZT would be something workers
could do to protect themselves."
Question: how accurate have been projections from five years
ago?
"From most reasonable people, projections have been
sometimes inflammatory, but they have been accurate at least in
pointing to where the epidemic is going. If you look at people
like Dr. Donald Francis, he has been quite accurate the whole
time. The conservative right, and some of the stories hyped in
the media, have often been wrong.
"Clearly we are seeing different diseases emerging as people
live longer. One reason is that antivirals may change the
natural course of HIV disease. We are prophylaxing against
pneumocystis, so people who were dying of it live to get
something else. And KS is going away by itself, for reasons we
do not understand.
"We're seeing more toxoplasmosis, more cryptococcosis, and a
lot more lymphoma.
"As in cancer, each person with AIDS is their own individual
case. Some people will do very well over time, but others with
the same laboratory tests will do poorly. The challenge
continues to be to find out what that difference is, so that you
can do for the ones doing poorly what the others are doing for
themselves.
ANNOUNCEMENTS
Parallel Track Letters Due July 20
Public comments are due by July 20 on the proposed "parallel
track" system to allow earlier access to experimental treatments,
for patients who cannot participate in clinical trials and have
no other treatment options. (For background on the parallel
track proposal, see AIDS TREATMENT NEWS #104, June 1, 1990.) It
has taken over a year for this proposal to wind its way through
government offices (NIAID director Anthony Fauci, M. D., called
for this system on June 23 of last year), and it is very
important that it now be adopted.
All letters on the parallel track are public information,
available to anyone who goes to the office in Washington (you can
write anonymously if you must keep your HIV status confidential).
Since the letters are public even before the comment period has
ended, we asked Garey Lambert, an investigative AIDS reporter for
The Baltimore Alternative, to check what responses had already
come in so that we could report the current status of the public
comments to the community.
When Mr. Lambert checked on July 6, 180 comments had been
received by the AIDS Program Office; about 80 percent of them
were form letters distributed by Mobilization Against AIDS. All
the letters received supported the parallel track -- a few with
reservations -- and many included suggestions for improvement.
Reservations/suggestions included:
* Opening the program to persons with other life-threatening
illnesses like cancer and Alzheimer's, not just AIDS.
* Making it easier for public clinics to use parallel-track
drugs, by allowing the clinics to qualify as organizations, so
that they can enroll patients who cannot afford private
physicians and do not see the same physician on every visit.
* Randomizing drug doses, to allow scientific efficacy
information to be obtained from the program.
* Allow patients otherwise eligible to enter the program if
they fail the standard treatments -- without requiring that they
also fail experimental therapies under the "treatment IND. "
What is important is to begin the program by accepting the
proposal which is now on the table. All of the suggested
improvements can be made later -- often withoug any formal change
in the rules.
Donald Abrams, M. D., submitted a survey of members of the
Community Consortium -- an organization of physicians and other
health-care providers who treat most persons with HIV in the San
Francisco area. Of the 38 who responded, 95 percent supported
the parallel track concept.
Despite the overwhelming support so far, acceptance of the
program is far from certain. Opposition is expected, and many
people seem to have waited until after the Sixth International
Conference to write their letters. It is especially important
that the National AIDS Program Office hear from physicians and
other health professionals, from organizations, and from persons
with HIV who do not have access to clinical trials due to medical
ineligibility or because there are no trials in their area.
Send comments to: Parallel Track Policy, National AIDS
Program Office, 200 Independence Avenue SW, Room 738-G,
Washington, DC 20201. For more information, call Dr. Valerie
Satlow or Donald Pohl at 202/472-4248.
ACT UP/New York Publishes AIDS Treatment Research Agenda
ACT UP/New York's Treatment and Data Committee released its
June 1990 AIDS Treatment Research Agenda at the Sixth
International Conference on AIDS in San Francisco. This
excellent 27-page document surveys what is and is not happening
in AIDS research, what must be done to improve it, and how you
can help. It combines ideas from leading scientists on how to
design better trials with real-world insights on overcoming
recruitment problems by designing trials that people want and
need. It names over 100 important experimental drugs, with the
highest priority ones listed separately.
To obtain a copy, write to ACT UP/New York, 496-A Hudson
St., Suite G4, New York, NY 10014, phone 212/989-1114. There is
no charge, but a contribution would be appreciated.
AIDS in Prison: Meeting July 18, Washington DC
A one-day Institute, "HIV/AIDS Education & Health Concerns
for Incarcerated Populations," will take place July 18 in
Washington, DC. Sponsors include Action AIDS-Philadelphia, ACLU
National Prison Project, National Lawyers' Guild AIDS Network,
Prison AIDS Education Program of Philadelphia Department of
Health, and others.
This Institute is part of the pre-registration program of
the 12th National and 3rd International Lesbian and Gay Health
Conference and the 8th National AIDS Forum, which runs from July
18-22; the conference theme this year is Developing Stronger
Networks. Registration is $55 for the Institute only, $25 with
registration for the gay health conference. The meeting will be
10 a.m. to 5:30 p.m. at the Washington Hilton, 1919 Connecticut
Avenue NW.
For more information on the Institute, call Paul Albert,
415/824-8884 or Judy Greenspan, 202/331-0500. To register for
the Institute or for the entire conference, call 202/994-4285.
California: State Budget Cuts Threaten AIDS Programs
A budget crisis in Sacramento threatens AIDS and other
health programs funded by the State of California. The problem
stems from an unexpected shortfall in State revenue, plus a
governor consistently unsympathetic to AIDS and other health
service programs.
At this time we do not know which programs are in danger,
and we do not have a single contact number for persons who want
to help. We suggest that California residents willing to work on
this issue contact their AIDS organizations for the most current
information. You can also call Governor Deukmejian's office,
916/445-2841, to register opposition to cutbacks in AIDS and
other health care.
San Francisco: Women and HIV Forum, July 23
On Monday, July 23 a panel of AIDS researchers, community
activists, and women living with HIV will provide information
about clinical trials and women. Panelists include Dr. Sandra
Hernandez, director, AIDS office San Francisco; Dr. Eric Goosby,
San Francisco General Hospital; Kim Corsaro, Project Inform; Dr.
Toby Dyner, Community Consortium; Dr. Rebecca Coleman, SFGH AIDS
Clinical Trials Group; Shirley Gross, Bayview-Hunters Point
Foundation (moderator); and Catherine Maier, San Francisco AIDS
Foundation (moderator).
The program is from 3 p.m. to 6:30 p.m. at the Women's
Building. It is wheelchair accessible; you can arrange
transportation and childcare by calling 415/564-8958.
For more information about the program, call the Community
Consortium's Community Coordinator, 415/821-3144.
San Francisco: Conference Abstracts at Healing Alternatives
Library
A complete set of the scientific abstracts published by the
Sixth International Conference on AIDS is available at the
Healing Alternatives Foundation library in San Francisco.
Healing Alternatives is located at 1748 Market Street (near
Valencia); call 415/626-4053 for hours or other information.
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