ddodell@stjhmc.fidonet.org (David Dodell) (10/08/90)
Courtesy of Scotty, root@ozdaltz.uucp:
AIDS TREATMENT NEWS Issue #112, October 5, 1990
phone 415/255-0588
ddI and ddC: The Call for Early Approval
Women and HIV: New Consciousness,World AIDS Day
ACT UP/San Francisco Splits; New Golden Gate Chapter Formed
ACT UP Announcements: New York Needs Donations, Equipment
after Fire; National, San Francisco Demonstrations,
October 6, October 9
ddI and ddC: The Call for Early Approval
by John S. James
On August 16, Martin Delaney of Project Inform wrote to
physicians at the Antiviral Drugs Division of the U. S. Food and
Drug Administration, to let the Agency know that in the coming
months, many activists would be asking that two experimental AIDS
treatments, ddI and ddC, be approved soon based on the data now
available, without waiting two years or more for long-term
trials currently under way to be completed. Interest in rapid
approval of these drugs has developed surprisingly quickly; in
San Francisco, for example, ACT UP/Golden Gate is planning a
major demonstration for October 9 (see announcement, below).
The idea of approving ddI and ddC now did not begin with
activists, however, but among leading physicians and researchers
familiar with the drugs. For months, a consensus has been
building among the researchers that both drugs would ultimately
be approved anyway; why not, then, consider approving them now?
What is new is that activists are taking this idea, which might
otherwise have remained as conversation at scientific meetings,
and placing it on the national agenda.
The issue of ddI and ddC is vitally important because there
are tens of thousands of people unable to use AZT, or no longer
able to benefit from it. In addition, among gay men, most HIV
infections occurred between 1979 and 19851, before the cause of
AIDS and ways to prevent transmission were widely known; since
the median time from infection to AIDS is about 10 years, many
people will become ill over the next several years. More
treatment options, including early treatment, are essential.
How good are ddI and ddC? The important data generated by
the ongoing large-scale controlled trials has not yet been
compiled and analyzed, let alone published; therefore, the
physicians, scientists, and other professionals involved in the
trials are reluctant to make public statements. But informal
conversations with those involved suggest a widespread consensus
that both drugs will be approved because they do have a role in
AIDS/HIV treatment, especially in combination with AZT and/or for
patients who cannot successfully use AZT alone. (For results of
earlier human studies of ddI, see recent article by Yarchoan and
others2; also see papers published by Reviews of Infectious
Diseases, July-August 19903,4,5,6,7; for background on human
trials of ddC, see papers from a February 3, 1990 San Francisco
symposium, published in May by The American Journal of
Medicine8,9,10,11,12,13,14,15,16). The available evidence is not
conclusive, but it is consistently positive.
Neither drug is risk free. Both can cause peripheral
neuropathy, and must be administered carefully to avoid or
control this side effect. In addition, ddI can cause
pancreatitis, which in a few cases has been fatal; blood tests
are necessary so that if this condition starts to develop, the
drug can be stopped or have its dose reduced before it causes
illness. ddC does not cause pancreatitis.
The new data, currently being accumulated in formal trials
and in the large ddI expanded-access program, seems unlikely to
change the current belief that these drugs can be beneficial to
many patients, and that side effects are manageable. The new
data will be analyzed before drug approval is given. Activists
are not seeking instant approval of ddI and ddC, but rather
approval in the near future, hopefully before the end of 1990. In
the three months until then, the data could be analyzed, if an
adequate effort is made.
No one wants unconditional approval regardless of the data
-- and presumably no one would deny approval regardless of the
data, either. Therefore the real issue is not whether these
drugs should be approved, yes or no. The real issue is how to
make the decision -- how to evaluate all existing information to
best respond to a public-health emergency.
The Traditional Way to Decide
Protocols for the major ddI and ddC studies, like most
clinical trials today, have provision for early termination of
the trial if early results show definitively that one treatment
arm is worse than others. A "data safety monitoring board"
(DSMB) meets privately at pre-set intervals and unblinds the
study, so that patients will not be continued on a treatment
which is clearly worse. Usually, of course, the DSMB decides to
continue the study. And in that case it seldom says anything
publicly about what results were found, so as not to bias the
trial, for example by causing patients on a treatment arm which
seemed inferior to drop out. Because of this secrecy, the public
cannot monitor what is happening within the DSMB, and must accept
its work on faith.
We do not know what criteria the DSMB will use to decide
whether or not to terminate the ongoing ddI and ddC studies. But
there are several reasons to be seriously concerned that the
business-as-usual approach, which is to make this decision
according to criteria spelled out long ago, when the protocols
were first designed, could lead to the wrong decision. And the
decision will be vitally important, because if the trials are not
terminated early, they could last for two years or more after
enrollment problems are overcome -- meaning that neither drug
will be approved for a long time.
The first potential problem is that when these trials were
designed, immunological and virological markers (T-helper counts,
p24 antigen) were less accepted by researchers than they are
today. Therefore the trials were designed statistically to
compare two or more arms based on rates of death or major disease
progression. That is why these studies require hundreds of
volunteers and are likely to last two years. AIDS progresses
slowly, so it takes a long time to accumulate enough deaths and
major opportunistic infections for statistically definitive
comparisons to be made -- no matter how good the drug being
tested may be. If the DSMB for each trial evaluates the interim
data based on the original protocol, instead of today's
knowledge, it is likely that neither study will be stopped, and
we will have to wait out the two years for these drugs.
Another concern is that, for statistical reasons, the
criteria for early termination for clinical trials are extremely
conservative. The statistical methods in common use require that
if you take an early look at a study's data, and might have
stopped the trial but in fact do nothing, then at the end of the
study, your claims for the drug must be weaker than they
otherwise could have been. Although this is difficult even for
researchers to understand, the unbelievable result is that just
looking at the data could cause a drug which otherwise would have
been declared effective to be declared unproven instead. (The
reason for this is that the overall procedure of the trial must
be designed to control the probability of erroneously accepting a
worthless drug, and the early look does add to the probability of
such an error. Therefore, the final criterion for ruling the
drug effective at the end of the study must be tightened, in
order to keep the overall probability of error within the limit
claimed by the trial's designers.)
The problem for us is that to minimize this effect, to
minimize the possibility of having to reject a drug which
otherwise would have been accepted, trial designers require
extremely severe standards for early termination of a trial,
making such termination unlikely. A drug must do much better to
cause a trial to end early, than to be considered proven
effective if the trial had been scheduled to end at that point.
Another fundamental problem is that the largest trials being
conducted now are testing ddI and ddC individually. But today it
is becoming increasingly clear that the best way to use these
drugs is in combination, such as ddC with AZT. Large studies can
take so long to get into operation that they become obsolete even
before they begin.
Another Approach: Lasagna Committee Standards
On August 15, the National Committee To Review Current
Procedures For Approval Of New Drugs For Cancer And AIDS
(commonly known as the Lasagna Committee, after its chairman,
Louis Lasagna, M. D.) issued its final report (see "Federal Panel
Seeks Drug-Approval Reforms," AIDS TREATMENT NEWS #110, September
7, 1990). The Lasagna Committee had been asked by then Vice-
President George Bush to recommend better ways to study and
approve drugs for life-threatening conditions, to make them
available more rapidly to patients who need them. The
Committee's recommendations are based on ten hearings held
between January 1989 and April 1990.
Of the Committee's 20 recommendations, the one most relevant
to ddI and ddC approval is number four, "The FDA Standard for
Effectiveness of New Drugs." Because of its importance, we
reproduce the entire recommendation here:
"Because of its special relevance to issues faced today in
developing new drugs for cancer and AIDS, the FDA needs to
pay particular attention to the congressional intent in
requiring substantial evidence of effectiveness prior to
approval of a new drug application (NDA), as described in
the Senate Report on the Drug Amendments of 1962:
"'The term "substantial evidence" is used to require that
therapeutic claims for new drugs be supported by reliable
pharmacological and clinical studies. When a drug has been
adequately tested by qualified experts and has been found to
have the effect claimed for it, this claim should be
permitted even though there may be preponderant evidence to
the contrary based upon equally reliable studies. There may
also be a situation in which a new drug has been studied and
its effectiveness established only to the satisfaction of a
few investigators qualified to use it. There may be many
physicians who would deny the effectiveness simply on the
basis of a disbelief growing out of their past experience
with other drugs or with the diseases involved. Again, the
studies may show that the drug will help a substantial
percentage of the patients in a given disease condition but
will not be effective in other cases. What the committee
intends is to permit the claim for this new drug to be made
to the medical profession with a proper explanation of the
basis on which it rests. In such a delicate area of
medicine, the committee wants to make sure that safe new
drugs become available for use by the medical profession so
long as they are supported as to effectiveness by a
responsible body of opinion and scientific fact.'
"By applying these principles, patients suffering from AIDS
and cancer will have available to them new drugs for the
treatment of their disease at the earliest stage at which
there is responsible scientific evidence to justify
marketing.
"The committee recognizes that, by making new drugs
available for marketing at this early stage, when there is
substantial evidence but not yet definitive evidence of
effectiveness, there is an attendant greater risk of serious
adverse reactions that have not yet been discovered. Cancer
and AIDS patients have made it clear to the committee,
however, that in light of the seriousness of the diseases
involved, they are willing to accept this greater risk.
Earlier approval of new drugs will mean that the patient
will bear greater responsibility, along with the physician,
for understanding and accepting the risks involved."
It may seem unreasonable to urge that new drugs for life-
threatening conditions like cancer and AIDS be approved when
"reliable pharmacological and clinical studies" conclude that
they work, but "preponderant evidence to the contrary based upon
equally reliable studies" concludes that they do not. Why should
it be national policy to approve a drug when there is such
uncertainty?
Other parts of the Lasagna Report provide background for
this recommendation. For example, from a section discussing
cancer drugs but which also applied to AIDS, "It is only after
initial NDA approval of the drug as a single entity that its full
potential is realized, because physicians are then free to use it
in combination with other drugs in accordance with their best
clinical judgment. While still under investigation, such
combination uses occur only infrequently and with little
opportunity for full clinical exploration."
Before the current law on drug approval was passed in 1962
(the law to which the long quote above applied), drugs only had
to be proven safe before they could be sold in the United States;
they did not have to be proven effective. Although some analysts
have estimated that we would be better off with that system than
with the present one (claiming that earlier and less costly
access to good drugs would more than balance the harm caused by
the useless ones), very few people want to go back to the old
system of not requiring efficacy proof, and politically there is
no chance of that happening.
But in recent years, proof of efficacy may have been taken
too far -- to the extreme of requiring academically satisfying
proof, unrelated to real-world concerns such as balancing cost
vs. benefit, or the feasibility of actually carrying out some of
the trials which are called for. The result is a price tag of
over $200,000,000 for each new drug approved -- money the public
pays one way or another in drug prices. The more serious price
is paid in lives of patients denied new drugs when no
satisfactory alternative treatments are available.
The Lasagna Committee has issued an authoritative call for a
more balanced and workable approach to developing treatments for
life-threatening conditions. "When there is substantial evidence
but not yet definitive evidence of effectiveness," critically
important drugs should be approved for prescription use, with
physicians properly informed of the state of the evidence.
The academic elegance theoretically available from rigidly
controlled trials has led to an assumption that all new knowledge
about drugs comes from formal trials, and that physicians merely
apply that knowledge to patients. In fact, medical progress
rests on two legs -- scientific studies and also clinical
experience -- and they must work together for best results.
(Note: the Congressional intent and Lasagna Committee
recommendation that a drug can be approved even when there is
"preponderant evidence" against it does not describe ddI or ddC.
The data on both of these drugs, while not conclusive, is
overwhelmingly favorable; see references, below.)
Early Approval and Clinical Trials
One argument against early approval of ddI and ddC -- we
think it is the strongest argument -- is that early approval
would probably result in the ending of the ongoing large-scale
controlled trials. As a condition for approval, the
manufacturers would of course be required to continue doing
studies; the FDA is already moving in the direction recommended
by the Lasagna Committee of approving critically important drugs
at the earliest possible time, with more of the efficacy research
being moved into the period after the drug is available by
prescription. But usually such early approval is granted after
phase II studies have finished -- either at the end of their
scheduled time, often about two years, or in extreme cases by
early termination according to the very conservative pre- defined
criteria applied by the DSMB, as discussed above. For ddI and
ddC, however, activists want the existing data to be evaluated
now, without waiting for the ongoing phase II trials to finish;
the drugs would be approved if there is substantial evidence of
their value.
Theoretically it would be possible to continue the existing
large-scale phase II trials of both drugs, even after approval.
But in practice, with ddI and ddC approved and with the growing
belief that combination therapy with AZT is usually best, many
patients, especially those not doing well in the trials, would
leave them to choose other treatment options. Therefore, the
existing large-scale controlled trials probably could not be
completed.
A similar issue arose when AZT was approved; the long-term
phase II trial was terminated early by the DSMB. At that time,
there were 17 deaths in the placebo group compared to only one in
the AZT group, a difference so great that it did meet the very
conservative statistical criteria for ending the study early. But
today, in retrospect, it seems clear that AZT is not that good;
the extreme difference in the death rates must have resulted
partly by chance. No one knows why so many patients in the
placebo group had died at that time. Some researchers have since
argued that they wished the study had been continued longer, so
that we could have had more conclusive proof of efficacy,
especially regarding long-term use. It has even been suggested
that the early end of the AZT trial was a tragedy, since we will
never have the data which it could have provided.
But the benefits of early approval of AZT far outweighed the
costs. The benefits included not only getting AZT to the study
volunteers in the placebo group, but also making the drug
available to thousands of others not in the trials. The approval
also opened up the field of combination studies, as the FDA
almost never approves trials using more than one experimental
drug at the same time. And the success of AZT greatly advanced
all of AIDS research, by ending the earlier fatalism: the idea
that no drug could possibly work to treat AIDS.
And today much more is known about ddI and ddC, especially
about dose, side effects, and long-term human use, than was known
about AZT when that drug was approved. But perhaps the most
significant difference between the current situation and that of
AZT is that if the analysis of all existing data (which activists
are now calling for) confirms that combination therapies such as
AZT and ddC are often better than any of the drugs alone -- and
we believe it is almost certain that this result will be
confirmed -- then it will mean that the ongoing large- scale
controlled trials studying these drugs alone are fundamentally
obsolete, since the treatment they are testing would be known to
be less than the best. If the benefits of combination treatment
are confirmed, then will it be worth sacrificing the interests
not only of hundreds of volunteers in the ongoing trials, but of
tens of thousands of others for whom existing treatments are
unsatisfactory, to get more data on ddI and ddC as single-drug
therapies which will never be widely used?
Early Approval and Industry Incentives
Another argument against early approval of ddI and ddC is
that approval is not necessary to provide access, which can be
done through the proposed "parallel track" system, or a similar
expanded access mechanism, to allow drugs to be used while the
controlled clinical trials proceed. Parallel track and
comparable approaches certainly need to be explored. Some people
suspect, however, that early approval of drugs for prescription
use, while research continues in post-marketing studies, may work
better than expanded access systems such as parallel track, for
the following reasons:
* We are in an emergency, and expanded-access systems will
take time to work out, including the all-important physician
education component. Consider how long it is taking to develop
parallel track, since that concept was first proposed. But when
drugs are approved for prescription use, the necessary systems
are already in place.
* Expanded-access systems may not have the flexibility that
physicians and patients want -- for example, to allow use of
drugs in combination.
* Paperwork and other difficulties often limit such programs
to private physicians, raising equity issues because the
treatments are not available to those who receive their medical
care in public clinics.
* Expanded-access programs like parallel track will not
happen unless the pharmaceutical companies which own the drugs
are willing to participate. But the companies may not have
enough incentive to put their products on parallel track. They
cannot be allowed to earn money on a program to distribute drugs
before marketing approval (since if they could, the program would
become tantamount to marketing approval, and would have no reason
for separate existence). Even recovering their costs from
parallel-track distribution is not feasible, as pharmaceutical
companies are unwilling to reveal what their costs are. And if
companies are pressured to participate, then they have incentives
to create restrictions which keep the programs small. Parallel
track might turn out to be a good idea, except for one problem --
that it seldom gets used in practice.
What does provide incentive to pharmaceutical companies? One
expert on clinical trials described the companies' approach
toward the FDA as, "Tell us what we must do, and that if we do it
we will get the NDA," (New Drug Application approval, meaning
permission to market the drug). The only incentive that counts
for pharmaceutical companies is getting their drug approved.
(And incidentally, bureaucratic dynamics may favor approval of
unimportant drugs which break no new ground over major
innovations.)
Therefore, a policy of the earliest possible approval of
critically important drugs for life-threatening conditions such
as AIDS and cancer -- the policy recommended by the Lasagna
Committee -- has a hidden future benefit, in addition to the
present benefit of making existing drugs available earlier to
patients. It creates incentive which extends throughout the drug
development process, all the way back to the earliest theoretical
and laboratory studies, for companies to bring their most
important drugs forward, to focus their research resources on
critical, life-saving drugs, instead of pursuing the me-too
products for existing markets, which consume so much effort
today.
References
1. Hessol NA, O'Malley P, Lifson A, and others. Incidence and
prevalence of HIV infection among homosexual and bisexual men,
1978-1988 [abstract #M. A. O. 27]. Fifth International
Conference on AIDS, Montreal, June 4-9, 1989.
2. Yarchoan R, Pluda JM, Thomas RV, and others. Long-term
toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or
AIDS- related complex. The Lancet. September 1, 1990; volume
336, pages 526-529.
3. Rosencweig M, McLaren C, Beltangady M, and others. Overview
of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on
adult patients. Reviews of Infectious Diseases. July-August
1990; volume 12, supplement 5, pages S570-S575.
4. Cooley TP, Kunches LM, Sanders CA, and others. Treatment of
AIDS and AIDS-related complex with 2',3'-dideoxyinosine given
once daily. Reviews of Infectious Diseases. July-August 1990;
volume 12, supplement 5, pages S552-S560.
5. Dolin R, Lambert JS, Morse GD, and others. 2',3'-
Dideoxyinosine in patients with AIDS or AIDS-related complex.
Reviews of Infectious Diseases. July-August 1990; volume 12,
supplement 5, pages S540-S551.
6. Valentine FT, Seidlin M, Hochster H, and Laverty M. Phase I
study of 2',3'-dideoxyinosine: Experience with 19 patients at
New York University Medical Center. Reviews of Infectious
Diseases. July-August 1990; volume 12, supplement 5, pages
S534-S539.
7. Richman DD. Zidovudine resistance of human immunodeficiency
virus. Reviews of Infectious Diseases. July- August 1990;
volume 12, supplement 5, pages S507-S510.
8. Broder S and Yarchoan R. Dideoxycytidine: current clinical
experience and future prospects -- A summary. The American
Journal of Medicine. May 21, 1990; volume 88, supplement 5B,
pages 5B-31S to 5B-33S.
9. Meng TC, Fischl MA, and Richman DD. AIDS Clinical Trials
Group: Phase I/II study of combination 2'-3'-dideoxycytidine and
zidovudine in patients with acquired immunodeficiency syndrome
(AIDS) and advanced AIDS-related complex. The American Journal
of Medicine. May 21, 1990; volume 88, supplement 5B, pages 5B-
27S to 5B-30S.
10. Bozzette SA and Richman DD. Salvage therapy for zidovudine-
intolerant HIV-infected patients with alternating and
intermittent regimens of zidovudine and dideoxycytidine. The
American Journal of Medicine. May 21, 1990; volume 88,
supplement 5B, pages 5B-24S to 5B-26S.
11. Skowron G and Merigan TC. Alternating and intermittent
regimens of zidovudine (3'-azido-3'-deoxythymidine) and
dideoxycytidine (2',3'-dideoxycytidine) in the treatment of
patients with acquired immunodeficiency syndrome (AIDS) and
AIDS-related complex. The American Journal of Medicine. May 21,
1990; volume 88, supplement 5B, pages 5B-20S to 5B-23S.
12. Pizzo PA. Treatment of human immunodeficiency virus-
infected infants and young children with dideoxynucleosides. The
American Journal of Medicine. May 21, 1990; volume 88,
supplement 5B, pages 5B-16S to 5B-19S.
13. Merigan TC and Skowron G. Safety and tolerance of
dideoxycytidine as a single agent. The American Journal of
Medicine. May 21, 1990; volume 88, supplement 5B, pages 5B- 11S
to 5B-15S.
14. Richman DD. Susceptibility of nucleoside analogues of
zidovudine-resistant isolates of human immunodeficiency virus.
The American Journal of Medicine. May 21, 1990; volume 88,
supplement 5B, pages 5B-8S to 5B-10S.
15. Broder S. Pharmacodynamics of 2',3'-dideoxycytidine: An
inhibitor of human immunodeficiency virus. The American Journal
of Medicine. May 21, 1990; volume 88, supplement 5B, pages 5B-2S
to 5B-7S.
16. Broder S. Dideoxycytidine (ddC): A Potent antiretroviral
agent for human immunodeficiency virus infection -- An
introduction. The American Journal of Medicine. May 21, 1990;
volume 88, supplement 5B, page 5B-1S.
Women and HIV: New Consciousness, World AIDS Day
by Denny Smith
December 1 will mark the third annual "World AIDS Day,"
sponsored by the World Health Organization (WHO). The focus this
year is on women and AIDS. In August, WHO estimated that of the
eight to ten million people with HIV infection around the world,
at least two million are women. Although women have played a
major role throughout the pandemic caring for others with AIDS,
their own HIV status and concerns have been trivialized or
ignored. A number of studies presented at the Sixth
International Conference on AIDS in June examined situations
faced by women, including unrecognized signs of HIV progression
and social barriers keeping women from early treatment. Several
of these studies and related upcoming events are discussed in
this article.
Examples of Inferior Diagnosis and Treatment
Within WHO's estimate of two million women with HIV, eighty
percent are cases reported from sub-Saharan Africa. Most of the
remainder are reports from Latin America and North America.
Eastern Europe and Asia document the lowest incidence, although
these are areas of the world least familiar with AIDS
epidemiology, so many cases may be missed. Women have become the
fastest-growing segment of reported HIV infections, but a
consequence of their marginalization in the epidemic is the
widespread incidence of undiagnosed or unreported infections.
Even where reporting is meticulous, biased assumptions discount
many people, such as lesbians and older women.
In the United States, a disproportionate number of women
with HIV are from communities of color, where AIDS is a leading
cause of death. In this country with the world's most reported
HIV diagnoses, health care is an elitist commodity, largely
available according to one's level of income. People with HIV
who are unable to afford private insurance have a difficult time
finding dependable care, and this inequity is worsened by
economic barriers of race and sex. A study presented at the
Conference by the Perinatal AIDS Center at San Francisco General
Hospital revealed that pregnant, HIV+ women experience social and
economic problems which pre-date their HIV infection and which
interfere with their compliance in clinical protocols and care
plans.1
The discrepancy between what women give to the health of the
community and what they get is not unique to the AIDS crisis.
Cultures everywhere rely on women to attend to the sick and to
details of daily health. A Conference report from Rutgers
University described results of interviews with care-givers of
people with AIDS that resembled social patterns of care for the
elderly and chronically ill: women provided the bulk of daily
care. More pointedly, people with AIDS in every transmission and
ethnic category received most of their unpaid care from women.2
This environment contributes to women putting their own
health second, with resulting delays in medical care and
increased susceptibility to opportunistic infections. An AIDS
information center in Mexico City, seeking ways to improve
psychological support for women with HIV, reported that women
with children always gave priority to the child, and second place
to themselves.3 A demographic review of a cohort of urban women
by Georgetown University Hospital found that women tended to
discover their serostatus late in HIV progression. Thirty nine
per cent of this cohort already had T-cell counts below 200, and
another 36 per cent had a count under 500.4 In other words, many
had missed the opportunity to intervene early, and probably more
effectively, in their infection.
The criteria for diagnosing AIDS have been defined largely
from studies of HIV progression in gay men, providing guidelines)
for physicians who may apply them to all their patients and
underrate symptoms like chronic vaginitis and pelvic inflammatory
disease specific to women. Gynecologic problems can be the first
signs of compromised immunity in women, and gynecologists may be
less likely than internists to be familiar with manifestations of
HIV. The Centers For Disease Control have been under pressure to
revise the definitions of AIDS to account for women's symptoms.
One concern receiving attention now is the frequency of
cervical and vaginal cell abnormalities which could develop into
tumors. A number of studies from the Conference, from different
countries, revealed a higher incidence of these in women with
HIV, especially those with past infections of the human papilloma
virus (HPV), which causes genital warts and is a sexually
transmitted disease. To monitor the risk of cervical cancers in
HIV+ women, some physicians now recommend pap smears every six
months.
A Conference abstract submitted by three German universities
described how alpha interferon production in women declined as
HIV infection progressed, and this was accompanied by an increase
in cervical and vaginal atypias and inflammation. They concluded
that the drop in alpha interferon production could give
predictive information for gynecological diseases.5
A number of factors may lead to lower survival rates in
women. An evaluation of people with Kaposi's sarcoma who attended
the Uganda Cancer Institute found that the incidence of KS was
increasing in general, and that women with KS tended to have a
more aggressive disease, involving lymph nodes, and died sooner
than male patients. The evaluators suggest that hormonal factors
be investigated for their role in the development of KS. 6 (In
other countries, KS is diagnosed less frequently in women than in
men.)
Pregnancy raises a variety of questions for HIV+ women, such
as the potential for transmitting the virus to the baby, the
effect of various drugs on the mother and the fetus, and the
effect of pregnancy on the mother's HIV infection.
The chances for infants to acquire HIV from seropositive
mothers has been reported recently to be 25 percent and lower, a
drop from older estimates. The modes for mother to infant
transmission are becoming better understood. Transmission is
thought to be possible through the placenta (perhaps at any time
of the pregnancy), during birth (contact with maternal blood),
or, least likely, after birth through breast feeding. Scientists
at the National Institute of Allergy and Infectious Diseases
(NIAID) discovered that several types of cells in the placenta,
like helper cells in the blood, exhibit a CD4 receptor to which
HIV readily binds. NIAID is conducting a clinical trial to
determine if AZT given during pregnancy can limit HIV
transmission to the fetus, although the protocol deals only with
the third trimester.
A French study at the Conference found that the incidence of
perinatal transmission is increased in mothers with low helper
cell counts and positive p24 antigenemia.7 This would imply that
early monitoring and antiviral intervention for women to halt the
decline of immune markers could also lower the incidence of
perinatal transmission.
A retrospective review of 403 women in Masaka, Uganda,
compared the progress after childbirth between HIV+ and HIV-
mothers. The seropositive mothers had longer hospitalizations,
lower mean hemoglobin levels, and an increased incidence of
thrush, herpes zoster, headaches and gastrointestinal upsets.8
However, among women who are seropositive, there is no
evidence that pregnancy speeds the progression of HIV infection.
Signs of Change
A new critical awareness of women's HIV health has generated
a sequence of events this year.
* At the International Conference on AIDS in San Francisco
last June, ACT UP staged effective demonstrations to highlight
issues pertinent to women with HIV, using civil disobedience to
block downtown city traffic and capture the eye of the news
media. More than 80 studies relating to women and HIV were
published in the Conference abstracts, a sign that these issues
have been receiving some private, if not public, attention.
Unfortunately, AIDS research has been so obsessed with women's
relationship to childbearing and transmission of the virus, that
data from studies of women's health for the sake of women are
still empty pages. We need news of options and experience for
treating women's HIV infections.
* In July, women and AIDS organizations around the San
Francisco Bay Area held a public forum addressing the deficits in
the design of clinical trials. Speakers included women living
with HIV, physicians treating AIDS, and community service
providers. The issues included clinical trials entry criteria,
which can arbitrarily exclude women based on the theoretical risk
of a new drug taken during pregnancy. Although the risk should
be considered, the choice is illogically removed from those with
the greatest interest -- potential women participants. Another
aspect of traditional trial design which can systematically
exclude women consists of protocols which try to minimize
variables in the data by recruiting from a homogeneous
population, such as gay men.
The head of the AIDS Activities Office of San Francisco's
Department of Health, Sandra Hernandez, M. D., who was one of the
forum's speakers, called for a reassessment of
inclusion/exclusion criteria for clinical trials, and a
realignment of their purpose and scope to account for everyone
coping with HIV.
* At a recent meeting of the AIDS Clinical Trials Group in
Bethesda, Maryland, Daniel M. Hoth, M. D., announced a future
public conference to address women and HIV, in collaboration with
the Centers for Disease Control. The announcement came after
months of pressure from AIDS activist women. Researchers from
NIAID then met with representatives from the AIDS community the
week of September 24 to plan the details of the conference. We
spoke with Lisa Auer, who was there representing the Project
Inform Community Research Alliance in San Francisco.
Ms. Auer told us that the meeting was productive, and
relayed some decisions about the conference: it will be held in
Washington, D. C. on December 13 and 14; four separate focus
tracks were named: epidemiology, clinical manifestations and
therapeutics, psychosocial aspects of HIV, and education and
prevention. Only 1000 participants will be registered, with 100
spaces reserved specifically for women with HIV. Attendance is
free, and for information interested persons can call Carol
Gordon or Debra Stewart at 301/770-0610. The next issue of
Project Inform's PI Perspectives will contain an article by Ms.
Auer on woman and HIV.
* New community models could facilitate women's access to
consistent health care. One example is a living cooperative for
women with AIDS or related conditions and their children now
organizing in Oakland, CA. The project is named Hale Laulima, a
Hawaiian expression meaning "house of many hands"; it should be
active by December. The goal is for residents to meet their
individual needs, such as doctor visits, by pooling resources and
sharing meal preparation and childcare. This could substantially
improve access to medical care for women ordinarily not able to
take time for their own needs. The residence also plans to
foster discussions of treatment information, which frequently
doesn't reach isolated women in a community. (Hale Laulima can
use financial donations -- the mailing address is 3871 Piedmont
Avenue, Oakland, CA, 94611.)
Another new community model was described in a Conference
abstract from the New Jersey Medical School and Medical Hospital,
where a full-service outpatient clinic for women with HIV was
established. When the course of women followed by the clinic was
compared to women seen only as hospital patients, the data
suggested that those cared for in the clinic had better survival
rates. The clinic provided psychological support and social work
services as well as medical attention.9
The New Jersey Women and AIDS Network has printed a very
useful brochure surveying the problems and answers pertinent to
HIV+ women, and a similar booklet written for health providers.
Requests for copies can be sent with a self-addressed stamped
envelope to the New Jersey Women and AIDS Network, 5 Elm Row,
Suite 112, New Brunswick, NJ, 08901. Their phone number is
201/846-4462. For bulk orders the brochure is 20 cents each and
the booklet is 30 cents.
The Women's AIDS Network, based in San Francisco, compiles
topical information packets for women and for organizations
dealing with HIV and AIDS. It can be reached at 415/864-4376,
extension 2007.
The AIDS activist community, women with HIV, and many AIDS
service-providers are calling for future AIDS research to address
women directly. HIV progresses in women, even if no one notices
until a serious crisis brings them to an emergency room, and even
while they are depended on to maintain the health of others.
Symptoms of HIV in women are late in gaining recognition, with an
according lag in effective treatments.
1990 is more than past the time to acknowledge the pivotal
position of women in the AIDS crisis, and begin to correct the
pervasive, institutionalized neglect of their health.
Information concerning World AIDS Day can be requested from WHO,
1211 Geneva 27, Switzerland. In the U. S., activities will be
coordinated by the American Association for World Health, which
can be reached at 202/265-0286.
References
1. Hauer LB and others. Client compliance with perinatal AIDS
research: the Bay Area Perinatal AIDS Center (BAPAC) experience
[abstract Th.D. 805]. Sixth International Conference on AIDS,
San Francisco, June 20-24, 1990.
2. Schiller NG and others. The role of kin in care giving for
persons with AIDS in New Jersey [abstract Th.D. 822]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
3. Tovar P and others. Psychological aspects and particular
problems in HIV infected women [abstract S. B. 374]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
4. Young MA and others. Natural history of HIV disease in an
urban cohort of women [abstract F. B. 432]. Sixth International
Conference on AIDS, San Francisco, June 20-24, 1990.
5. Friese K and others. Interferon alpha as a predictive
parameter in the development of gynecological diseases in HIV-
infected women [abstract F. B. 461]. Sixth International
Conference on AIDS, San Francisco, June 20-24, 1990.
6. Mbidde EK and others. The epidemiology and clinical features
of Kaposi's sarcoma (KS) in African women with HIV infection
[abstract S. B. 508]. Sixth International Conference on AIDS,
San Francisco, June 20-24, 1990.
7. Boue F and others. Risk for HIV-1 perinatal transmission
vary with the mother's stage of HIV infection [abstract Th.C.
44]. Sixth International Conference on AIDS, San Francisco, June
20-24, 1990.
8. Kalibala S and others. The relationship between HIV
infection and maternal morbidity in Masaka, Uganda [abstract F.
B. 458]. Sixth International Conference on AIDS, San Francisco,
June 20- 24, 1990.
9. Pinto RC and others. Women's clinic: a full service clinic
for women with HIV disease [abstract S. D. 816]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
ACT UP/San Francisco Splits; New Golden Gate Chapter
by John S. James
On September 13, about a third of the 200 members of ACT
UP/San Francisco left the group and formed a new organization,
ACT UP/Golden Gate. The split was covered remarkably well in the
three major San Francisco gay newspapers (the Bay Area Reporter,
the Bay Times, and the San Francisco Sentinel), in the general-
interest SF Weekly, and later in one of the major daily
newspapers, the San Francisco Examiner (October 1). We will not
repeat their detailed information; but since we will be reporting
on b{oth groups in the future, we included this sketch of what is
happening and why.
The split came after months of increasing tension, and many
people think the division will be beneficial. Both organizations
are now working well, and they have begun their relationship on
good terms. Some individuals will be active in both, and weekly
meeting nights have been arranged to accommodate. One committee,
the Youth Action Caucus of ACT UP/San Francisco, applied to also
be a committee of ACT UP/Golden Gate, and was accepted. The
groups are expected to work together; for example, both
unanimously endorsed a call for approval of ddI and ddC before
the end of the year.
Why, then, the split? The immediate issue was whether to
maintain consensus, or allow decisions by an 80 percent vote. The
decision to adopt voting would have had to be made by consensus,
and when several people blocked that decision, the group split.
(ACT UP/Golden Gate now makes decisions by a two-thirds vote,
although in practice many, if not most, are unanimous.)
For both groups, demonstrations and street theater are
primary tools. But ACT UP/Golden Gate also emphasizes working
"within the system," as well as on the street, to get research
done and make treatments available, and those who work with
government agencies, pharmaceutical companies, and other
mainstream organizations, want group support. ACT UP/San
Francisco emphasizes the need for larger social change to end the
epidemic, as well as the need for treatments. Consensus was a
key issue, because giving anyone the power to block group action
assured that minority voices would be heard and considered. But
with 200 members with very diverse points of view (ACT UP/San
Francisco had tripled in size since the June, 1990 Sixth
International Conference on AIDS), it had become very difficult
to get any significant action approved. Energy was increasingly
devoted to process issues and infighting, instead of useful work.
Separation has freed both groups, ending paralysis, allowing
productive competition, and opening the way for members who had
previously left the group to now return to one or the other. Both
groups will hold demonstrations in the next week (see
announcement below).
The general meeting of ACT UP/San Francisco continues to be
every Thursday at 7:30 PM at the Women's Building, 3543 18th
St. (near Valencia). ACT UP/Golden Gate meets every Monday at
7:30 at 347 Dolores St., room 202.
ACT UP/New York: Donations, Equipment Needed after Fire
A recent arson fire caused $100,000 damages to the new
workspace of ACT UP/New York. Much of the equipment lost was
insured, but the insurance will not be paid until the fire
investigation is complete, which could take months. Donations of
money and equipment (especially Macintosh computers) would be
appreciated. Checks should be payable to ACT UP; send them to
the new address: ACT UP/New York, 135 W 29th St., #10, New York,
NY 10001. The new phone number is 212/564-AIDS. The fax number
remains the same, 212/989-1797.
ACT UP Demonstrations October 6 and October 9
(1) October 6, Nationwide
This Saturday, October 6, ACT UP groups around the country
are calling demonstrations to support funding for the Ryan White
CARE Act for AIDS disaster relief. As described in our last
issue (AIDS TREATMENT NEWS #111), a Senate committee provided
only a fraction of the money authorized in the law signed by
President Bush. The money was to go to cities and rural areas
most affected by AIDS.
Cities with demonstrations planned include, Baltimore,
Chicago, Columbus, Denver, Kansas City, Milwaukee, Minneapolis,
New Orleans, Oklahoma City, Phoenix, Pittsburgh, Portland, Los
Angeles, Sacramento, and Wichita. A demonstration is also
planned in Orange County, California. For more information, call
your local ACT UP; or for national information, call Saundra
Johnson, ACT UP/Chicago, 312/829-6797, or fax to 312/975- 8468.
On the Saturday of the demonstration, media can call 312/327-
7015.
In San Francisco, ACT UP/San Francisco is coordinating the
demonstration; it has also been endorsed by ACT UP/Golden Gate.
The march will begin at 7: 30 p.m. at the ARC/AIDS Vigil at
United Nations Plaza, then proceed up Market Street to the
Castro, for a rally and street theater. For more information,
call ACT UP/San Francisco at 415/563-0724.
(2) October 9, ddI and ddC Demonstration, San Francisco
On Tuesday October 9, ACT UP/Golden Gate will coordinate a
demonstration for approval of ddI and ddC, at the FDA regional
office at noon (see "ddI and ddC: The Call for Early Approval,"
above). One of the slogans for this action, expected to include
street theater, is "ddI and ddC or DOA!!" A press conference will
be held at 9: 00 a.m. ACT Up/San Francisco has also endorsed
this demonstration.
For more information, call J. C. at 415/995-4536 (day) or
415/255-7746 (evening), or G'dali Braverman at 415/252-5689.
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