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New Approaches to HIV Treatment: Interview with Robert
Gallo, M.D.
by John S. James
Robert C. Gallo, M.D. is Director of the Institute of Human
Virology, located at the University of Maryland in Baltimore.
The Institute focuses primarily on AIDS research; it was
started in 1996 with start-up funding from the State of
Maryland and the City of Baltimore. We asked Dr. Gallo to
discuss some of its current research projects.
AIDS Treatment News: First, could you give our readers a
sense of the mission and focus of the Institute?
Dr. Gallo: The Institute's focus is experimental medicine, to
bring discovery from the laboratory to the clinic. It is not
a basic science institute, but it does include basic science.
Our main mission, aside from preventive AIDS vaccines, is
continued study of the biology of HIV and the host response,
and the mechanisms involving their interaction that lead to
disease processes; this is commonly called pathogenesis. From
these studies we look for findings that have potential
clinical uses. We also do some research on cancer, multiple
sclerosis, and a few other diseases, but about 80% of our
work is in AIDS.
We have people studying the molecular biology of HIV, and
also a variety of herpes viruses that are relevant to HIV
disease. Others are studying the immune response to
infection. One unit, about five people now, is working on
chemokines and their receptors. [Note: Chemokines are
chemicals produced by the body which attract certain immune
cells to the sites of various infections and which, as Gallo
and his co-workers discovered in 1995, can be natural
inhibitors of HIV.] Another unit, investigating the
pathogenesis of Kaposi's sarcoma, overlaps us with the clinic
and links us to the cancer center of the University of
Maryland; this group is attempting to purify a protein from
the urine of pregnant women, which we now call HAF [see
below]. We also have a molecular endocrinology unit that
studies the role of hormones in a variety of diseases, headed
by Dr. Bruce Weintraub, M.D., who used to head a similar
division of a laboratory at the U.S. National Institutes of
Health (NIH). We brought in a number of people from NIH.
That gives you a flavor. The vaccine program is fairly large,
the clinical division is very large, and has established
outreach to nearby hospitals. A diagnostics division will try
to refine some of the viral quantitation and other
diagnostics, not only limited to HIV.
We have excellent facilities, 100,000 square feet of modern
laboratory space in a 200,000 square foot building in the
center of Baltimore. We are within the complex of the Medical
Center of the University of Maryland, so the university
hospital is about a block away. Also nearby is the Veterans
Administration hospital, which is also part of the University
complex.
The Institute of Human Virology has been in operation for
about a year now.
ATN: How is its work funded?
Dr. Gallo: We received three years of funding, $12,000,000
total, from the state of Maryland and the city of Baltimore.
Maryland's Governor Glendening, whose brother died of AIDS,
has been very supportive. He was a former professor here at
the University of Maryland. His push led to this Institute;
he played a leadership role. And Baltimore mayor Kurt Schmoke
has a deep concern about AIDS here in the city.
After the three-year period we will have to hustle like
everybody else, with less state support and no longer city
support.
We are obligated by our contract with the State of Maryland
to try to form a biotechnology company. This is a change from
the early years, when such things were frowned on; now they
are important. The company will help us go from the lab to
clinic; hopefully it will allow us to make some of our
projects self-funding, as we are spending far too much time
on money issues now.
We do not have an endowment; there is no person's name on our
Institute of Human Virology. We are looking for that kind of
endowment, which would give us the flexibility to follow up
on important developments immediately, without waiting to
bring NIH funds in.
ATN: How is the Institute organized administratively?
It is divided into five divisions. They are: Basic Science,
headed by me; Clinical Virology, headed by Robert Redfield,
M.D., from Walter Reed, and forming a unique division within
the University of Maryland School of Medicine; Epidemiology
and Diagnostics, by William Blattner, M.D., from the National
Cancer Institute; Vaccine Research, essentially 100% HIV
preventive vaccines, headed by cellular immunologist George
Lewis, Ph.D.; and Animal Models, by Joseph Bryant, D.V.M.,
also from the National Institutes of Health.
These five divisions are all coordinated and overlapping,
working and meeting together. Dr. Redfield has an HIV
outpatient department not only in the hospital, but also
right in this building, which I believe is unique for a
research building.
ATN: What are some of your own projects at this time?
Dr. Gallo: My personal chief focus is trying to develop
biological approaches to contain HIV in a person already
infected. Sometimes, perhaps most of the time, this involves
the manipulation of or targeting of a cellular factor.
Remember that viruses in general need cells to replicate;
they are not like bacteria, fungi, or protozoa, in that
viruses cannot reproduce outside of a cell nor do they have a
metabolism of their own.
One has to be more subtle in targeting a virus, therefore,
because a virus mostly uses the host cell mechanisms to
reproduce itself, more than the protein products encoded by
the viral genome. So we try to think of cellular factors that
the virus will need more than the cell, so that if you
inhibit them somewhat, you might avoid toxicity, but
interfere with the virus. There also could be less chance of
escape mutations with this approach [than with ordinary
antiretroviral drugs], because the human cell does not mutate
like the virus.
We also feel that such research would open novel areas. The
pharmaceutical industry is already well set up to target the
enzymes of the virus; we could not even begin to compete with
them there. What are needed are new avenues, new ideas, new
approaches, and these are what we try to do -- to think of the
way the virus uses the cell to reproduce itself and how it
causes disease.
An example would be the levels of the building blocks for
making DNA inside the cell. The HIV enzyme that makes DNA --
reverse transcriptase -- needs a higher concentration of the
building blocks of DNA, the nucleotide pool, than does our
cellular DNA-making machinery. We argued years ago that if we
could lower the building blocks for DNA modestly, we might
avoid toxicity but interfere with HIV. That led to the
hydroxyurea trials.
Another cellular factor most HIV variants need is the CCR-5
receptor, to enter macrophage-type cells, at the beginning of
infection. By blocking it with the chemokines RANTES, MIP-1a
and MIP-1b (which we found are potent inhibitors of these) --
you might stop early infection.
This approach might also help in later infection, but then
you would need something else in addition to protect the T-
cells as well.
MDC (Macrophage Derived Chemokine)
Dr. Gallo: We recently discovered that MDC, another
chemokine, also specifically blocks HIV -- not limited to the
virus which infects macrophages, but all types of HIV. We
hope that it can go into the clinic as we learn how to mass-produce this substance and rule out any unwanted toxic
effects -- or modify the molecule if necessary so there would
not be any inflammatory toxic effects. This is one of our
main lines of research today.
How does MDC work? The other chemokines seem to work by
simply binding the receptors. The evidence is very strong
that this binding downregulates the number of molecules on
the cell surface [making it harder for the virus to enter a
cell, if it needs to use those molecules for entry].
However, MDC works against all the variants of HIV that we
have studied. It cannot be just by blocking. But there is
some precedent for factors binding to their receptors and
down-regulating nearby receptors. We suspect that when MDC
binds by some mechanism, it downregulates all of the
chemokine receptors. Ongoing work here now is investigating
the molecular mechanism. Work by my colleague Tony Devico and
also Alfredo Garzino-Demo is focused fully on these
questions.
We are trying to bring such chemokine studies into primates
now; that is work of Fiorenza Cocchi, who was the lead author
of the first paper showing that some chemokines block HIV
infection (the macrophage tropic HIV variants), the RANTES,
MIP-1a, and MIP-1b paper.
We are also studying chemokines and rates of progression to
disease. Will their levels help to predict progression? So we
are also asking whether chemokines could be immune correlates
of an effective vaccine -- in addition to our program to try to
bring them to therapy.
These are the kinds of projects it is hard to get funding
for -- the obvious questions, the applied questions. It is
strange but true.
ATN: What does get funded instead?
Dr. Gallo: The NIH grants need to be hypothesis-driven, to be
more fundamental. If you have something that you think is
ready to bring to the clinic, there is usually not a grant
mechanism for that, at least not with enough money to do a
small clinical trial -- and to develop the approach by doing
the pharmacokinetics, and doing monkey studies. Although this
work is obviously important, there is not money for it in the
usual NIH granting mechanisms.
We are also looking at combining part of one chemokine
receptor with part of another, so that the final receptor is
a mixture, or chimera. And the same with chemokines
themselves. We are empirically testing to see what effect
some of these chimeras can have.
We are interested in uninfectable people. Do some of them
overproduce chemokines, not just have receptor mutations?
ATN: What are you learning about HCG and Kaposi's sarcoma?
[Note: HCG, human chorionic gonadotropin, is an approved drug
today, and is being studied as a potential KS treatment. It
is obtained from the urine of pregnant women.]
Dr. Gallo: We are trying to identify a protein -- not HCG --
which is found in the urine of women in the first weeks of
pregnancy. This unknown substance is found in some commercial
preparations of HCG, as a contaminant. So if you use HCG for
treating KS, it is like a needle in a haystack -- using the
whole haystack to give you the needle. This makes clinical
results difficult, and almost meaningless if you get a
negative result. How much of the drug do you use? How should
you administer it? All these are unknowns when you are
dealing with such a crude mixture, most of which has nothing
to do with what you want.
Obviously the goal is to purify this unknown substance. Again
we face a serious practical problem -- who funds collecting
large amounts of urine, concentrating the urine, purifying
the protein? We are talking to NIAID (U.S. National Institute
of Allergy and Infectious Diseases) about it; they have been
very good in listening and advising and trying. But in the
end, these practical ideas are the hardest to get funded.
We have called this protein HAF -- HCG-associated factor. This
name will only be temporary. When we identify the protein, it
will get the right name. It is possible that the substance is
already known, but not used before in this context.
Where are we with this research? In collaboration with Steve
Birken at Columbia University we have started to purify the
molecule; and so far, it has multiple activities. You could
argue that since it is not pure, there could be different
molecules for each of these activities. I don't think so,
because they are co-purifying, so far, through quite a number
of steps.
Promoting the growth of normal bone-marrow cells -- as opposed
to being toxic to these cells, which most chemotherapy is.
And there is also an antiviral effect, but its mechanism has
not yet been worked out.
What is the status today? People are using HCG which has been
pre-tested to show that HAF is present. And we know there is
benefit to some people with Kaposi's sarcoma.
When we purify HAF we will have the right molecule. That
could be much more potent, unless we begin to lose activity
in purification by modifying the molecule. But once it is
stabilized, this substance should be thousands of times more
active [than the HCG preparations which are commercially
available today].
ATN: When do you expect to identify the active molecule?
Dr. Gallo: We hope that in 1998-1999 we will have achieved
our goal. We have major collaboration with the protein
chemistry core facility at Columbia University, and its head,
Dr. Birken, He is into the problem, and he is one of the best
in the world for this type of problem. We hope that within a
year, the substance will be purified, and we move on to the
IND [permission from the FDA to test a new drug in humans],
after doing the toxicology and other preclinical work.
ATN: We have heard that changes at the FDA may make the drug
development easier.
Dr. Gallo: That would be great for us.
We are also going to re-start some of the studies of the
hydroxyurea mechanism. Dr. Redfield wants to bring it here
clinically. We want to know why it synergizes more with ddI
than AZT. Our hypothesis was that it would synergize with
both -- but yet I hear it does not with AZT. That is peculiar;
it needs to be understood.
HHV-6 (Human Herpes Virus 6)
Dr. Gallo: We are also studying a virus we discovered ten
years ago, herpes 6. What is it doing, if anything, in late-stage HIV infection? Most people are infected with this
virus. But in the lab, it is very potent at harming T-cells,
when it is actively replicating. In most people it is not
replicating. But in some HIV-infected people, it is.
How can we demonstrate that it is having a harmful effect?
The only way I know is to find a specific inhibitor of this
virus. Here we need collaboration with a drug company. We
have not established that yet. We have tried; people were not
interested for AIDS. They were also not interested in the
infant disease roseola, which this virus causes. Maybe now
that researchers at NIH are claiming that HHV-6 plays a role
in multiple sclerosis there will be more interest.
Protecting Uninfected Cells
Dr. Gallo: In another area, we have a substantial
collaboration with Daniel Zagury, of the University of Paris.
Here the goal is to try to "de-narcotize" the uninfected T-cells in HIV-infected people. The mass of T-cells, as you know, are not infected; but their ability to grow is
inhibited. We think we understand part of the reason -- that it
has to do with an HIV protein that is excreted that has this
effect, as well as certain cytokines, especially alpha
interferon, which are overproduced in HIV-infected people.
We have a way to lower the levels of these molecules. In the
laboratory, this restores the ability of T-cells to grow
properly. Dr. Zagury has already brought this approach to
clinical trial. For the last four years he has been lowering
the levels of alpha interferon by a vaccination program,
i.e., he actually vaccinates against this normal but over-produced cytokine by denaturing it and making it immunogenic.
He is also starting clinical trials to lower the level of
some HIV-secreted proteins [such as tat], which may work as a
toxin to cells at a distance. We are trying to get funding,
about half a million dollars, to bring a clinical trial here
to Baltimore as quickly as we can.
ATN: One question on this technology: How do you vaccinate to
lower the level of something that is already in the body?
Dr. Gallo: You make a denatured form of it, that is
immunogenic when you test it. You have to test it in humans.
In this case it worked. If you modify something, put the same
molecule in a different configuration, you can generate
antibodies against it; the body sees it as foreign. So you
look for a way of doing this that also creates an immune
response against the original molecule. The approach is
unorthodox, but it is not novel. Therapeutically it may be
novel.
We were talking with a company this month about funding. We
have argued that their current immunological approach to
stimulate the immune system with HIV "fragments" (cores)
might be greatly improved if the relative anergy of the
uninfected T cells can be overcome. I believe this is
possible with the approach we are involved in with our
collaborator, Daniel Zagury, in Paris, i.e., reducing
interferon alpha and the HIV-1 tat protein by vaccinating
against these molecules. [Otherwise] it is not likely to be
very effective. We are trying to think of ways that NIH could
help fund a program which combines these two approaches.
We will form our own biotech company; our contract with the
State of Maryland requires us to do that. So far it has been
slow to get this company going, mostly because of extreme
caution in the university; committees have to evaluate each
step.
ATN: What are your hopes for the future of the Institute?
Dr. Gallo: The new Institute of Human Virology will allow us
to directly bring our research into clinical testing. This is
the first time in my career I have been in this position. We
hope that in future years we will have left behind an
international research center of first class, one that
contributes to its community, and hopefully contributed to
the end of AIDS.
1592 (Abacavir): Do Not Rechallenge After
Hypersensitivity Reaction
by John S. James
In the experience to date with the experimental
antiretroviral abacavir (1592U89), about 3% of patients have
developed a systemic hypersensitivity reaction. Initially
this reaction is usually not severe and will go away by
itself within a couple days of stopping the drug. But if it
does occur, the patient must not try the drug again; if they
do, a serious and potentially life-threatening condition can
develop within hours.
The initial reaction usually begins from a few days to four
weeks after starting abacavir. At first there is low-grade
fever, nausea (with or without vomiting), and malaise (not
feeling well, as with the flu); these symptoms build up over
a few days. There is usually a rash, although sometimes it is
not noticed by the patient. As soon as the fever and flu-like
symptoms occur, the drug must be stopped, or the symptoms
will become increasingly severe. After discontinuation the
symptoms will disappear rapidly, and there seems to be no
further problem, as long as the patient never tries the drug
again.
But when abacavir has been tried again, high fever, severe
nausea and vomiting, and rash (not severe) have developed
within hours. In four of these cases there was life-
threatening low blood pressure. These patients were
hospitalized with intensive care. No deaths have occurred.
This problem appears to be entirely manageable by recognizing
the small percentage of patients who cannot tolerate abacavir
and must stop using it permanently. (Those who discontinue
for other reasons may be able to re-start.) Glaxo is planning
research to determine the mechanism of action of the
hypersensitivity, which currently is unknown. At this time
there is no way to predict which patients are likely to
develop it. About 2,000 people have taken abacavir so far,
and the drug's overall safety appears to be good. Clinical
trials continue to accrue patients and the abacavir
development program continues unchanged.
Glaxo Wellcome is educating physicians, researchers, and
volunteers in clinical trials about abacavir
hypersensitivity; information has also been shared with the
FDA. Anyone suspecting that they have developed
hypersensitivity to abacavir should speak with their
investigator or physician immediately.
Adefovir dipivoxil (trade name PREVEON), an experimental
antiretroviral, is now becoming available through a limited
expanded access program for some patients who have failed
approved treatments. This program will be important primarily
for those who need to start more than one new antiretroviral,
in accordance with current therapeutic guidelines.
Adefovir is a prodrug of PMEA, which has been discussed as a
potential antiretroviral for many years. (PMEA should not be
confused with the related but more powerful PMPA, currently
in phase I/II trials as an experimental treatment for HIV;
both PMPA and adefovir are being developed by Gilead
Sciences, of Foster City, California.) PMEA is in a class of
drugs called nucleotide analogs (distinguished from
nucleoside analogs such as AZT, ddI, or d4T); nucleotide
analogs need less processing by the body to be changed into
their active form.
Early results from phase I/II trials have shown that adefovir
alone has modest anti-HIV activity (about an average half-log
to 0.7 log reduction in viral load), but is active against
virus which has developed resistance to AZT, 3TC, and other
approved nucleoside analogs. Little or no HIV resistance to
adefovir has been found in patients so far. Adefovir also has
activity against CMV and a number of other herpes viruses,
and against hepatitis B; it is currently in trials to test
for these uses. It is taken as a capsule once a day (at the
same time each day), with or without food. It needs to be
combined with L-carnitine, a nutritional supplement which
will be supplied by this program, because adefovir has been
found to reduce L-carnitine levels in the blood in previous
trials. The side effect of greatest concern at this time is
kidney toxicity; Gilead requires monthly blood and urine
tests to detect this or other problems early.
To be eligible for the new expanded access program, a patient
must be at least 13 years old, have failed at least two
nucleoside analog RT inhibitors and one protease inhibitor,
and within the last two months have had a CD4 count of 50 or
less, and a viral load of at least 30,000 by PCR (the
Hoffmann-La Roche test) or at least 15,000 by bDNA (the
Chiron test). Patients must not qualify for other open trials
of adefovir. They must not be pregnant, and both men and
women must be willing to use contraceptives to prevent
pregnancy. There are several other laboratory criteria,
including serum creatinine less than or equal to 1.5 mg/dL,
and urine protein less than or equal to 1+. Patients are
permitted to combine other experimental antiretrovirals with
adefovir (including efavirenz, and 1592).
Only the adefovir and the L-carnitine will be supplied by
this expanded access program; all other expenses, including
laboratory tests and doctor visits, "will be the
responsibility of the patient."
Community Concerns
The two concerns we have heard at this time are the potential
kidney toxicity with long-term use of the drug, and also the
CD4 and viral load restrictions on entry into the program.
In clinical trials to date, a serum creatinine level of 2.0
or above has been seen in about 4% of patients who have
received the drug for six months or more; this problem seldom
develops in the first four months. The reason for the concern
is that experience with other drugs has shown that serious
kidney damage can occur before there are obvious clinical
symptoms. The danger is that as adefovir becomes more widely
available, doctors and patients may become complacent after
seeing no problems for several months, and skip the
laboratory testing. The expanded access program requires
monthly laboratory tests, including serum creatinine, urine
protein, and urine glucose. (The urine tests can also be done
at home, with dipsticks which are commonly used by diabetics,
in addition to the monthly testing in the doctor's office.)
At this time Gilead is using a cutoff of 2+ on the urine
protein test, and 2.0 or above on serum creatinine, to
identify those at higher risk of renal complications. Also,
glucose in the urine could be a sign of kidney toxicity. Any
of these laboratory abnormalities requires prompt evaluation,
and probably drug discontinuation or dose reduction. So far
the abnormalities have been mild to moderate, and reversible
when the drug was stopped or the dose reduced.
The most common side effects of adefovir are
gastrointestinal, including nausea and vomiting. Sometimes
these less serious problems are managed by reducing the 120
mg per day dose to 60 mg per day. Guidelines for dose
reduction will be provided to physicians.
Community advocates are also concerned about the current
restriction of this program to patients with a CD4 count
under 50 and a viral load over a cutoff value. The program
also requires that "the treating physician is unable to
construct a viable combination of antiretroviral agents for
therapy based on current treatment guidelines and the
patient's previous antiretroviral agent use"; advocates want
this kind of criterion only, without the specific CD4 or
viral load numbers, to allow physicians flexibility to put
together the strongest possible new antiretroviral
combination for a patient after previous treatments have
failed. There will be a procedure for requesting exemption
from certain entry requirements, when there is a strong
medical reason for doing so.
For More Information
For more information about the adefovir expanded-access
program, call Gilead Sciences at 800-Gilead-5 (800-445-3235);
press ‘1’ when requested by the voicemail. The office is open
8 a.m. to 5 p.m. Monday through Friday Pacific time.
For more information about clinical trials with adefovir
dipivoxil, call the AIDS Clinical Trials Information Service,
800-TRIALS-A; or call 800-GILEAD-5 and press ‘3’ on the
voicemail. The largest clinical trial at this time is CPCRA
039, now open in about a dozen U.S. cities, adding adefovir
or placebo to a stable antiviral regimen in patients with a
low CD4 count (usually 100 or less).
San Francisco: Eviction Legislation Protects Some with
Major Illness
On December 15 the San Francisco Board of Supervisors passed
an 18-month moratorium on "owner move-in evictions" of
persons with catastrophic illness who had lived in their
residence for five years or more. The law also covers persons
who are 60 or older, or disabled, with 10 years residency in
their unit. It was passed by a vote of 8-0 despite furious
opposition from landlords, who are likely to go to court to
try to block it. The law does not apply to single-family
homes, or to evictions to move in a relative over 60.
According to ACT UP/Golden Gate, owner move-in evictions have
increased over 400% in San Francisco in the last year, and
many people with AIDS have been losing their housing. Often
the vacated units are converted to condominiums or tenant-in-common ownership.
New York: One-Day Treatment Information Forum, January
17
A one-day presentation on new treatment information will take
place Saturday January 17 at the New York University Medical
Center (Farkas Auditorium), East 31st Street and 1st Avenue,
New York City, from 10 a.m. to 4 p.m. Admission is free and
refreshments will be served, but advanced registration is
required. This meeting is sponsored by the National AIDS
Treatment Advocacy Project (NATAP), the Center for AIDS
Research, and New York University Medical Center, and
cosponsored by many other organizations.
Topics include HIV therapy overview, pathogenesis, the brain
and HIV treatment, latent virus and lymph tissue,
opportunistic infection prophylaxis today, and thymic
transplant research for HIV.
To register, call 888-26-NATAP or 212-219-0106, 10 a.m. to
6:30 p.m. Monday through Friday, or fax to 212-219-8473.
Health Insurance Portability and Accountability Act
275
Healthcare Communications Group
275
Henry, Dr. Keith
281
herpes
264
herpes, acyclovir resistant
283
Herzenberg Laboratory
266
HHV-6
285
hit hard hit early
282
HIV InSite
284, 275, 267
HIV Medicines for Guatemala
280
HIV Prevention Act of 1997
276
HIV-specific CD4+
284
HMOs
280, 278
Ho, Dr. David
282
Hoffmann-La Roche
270, 268
hotlines
274
Houston
270
hypersensitivity
285
ICAAC
281
IDSA
277
IDSA Conference, 1997
279
IFARA
281
IL-2
272
immune-based markers
267
immune-based treatment
272
Immunet
284
immunology
284
indinavir
269, 266
Infectious Diseases Society of America
277
"information purgatory"
264
infusion pumps
282
Institute for Human Virology
285, 284
integrase inhibitors
282
international
280
International AIDS Vaccine Initiative
270
International Conference on AIDS Wasting
281
International Conference on AIDS Research
269
International Conference, 1998
283
International Foundation for Alternative...
281
Internet
281, 278, 275, 274, 271,
270, 267, 264, 263, 262
Internet -- Federal sites
275
IRBs
283
Irvine, CA
270
JAMA
275
Johns Hopkins University
275, 264
Kaposi's sarcoma
285, 277
kidney toxicity
285
L-carnitine
285
Lalezari, Dr. Jay
283
Lands, Lark
268
Lane, Clifford
272
linezolid
281
live vaccine
280
Loftus, Rick
264
Los Angeles
270, 265
Lymphoma Action Group
284
MACS database
264
managed care
280, 278, 277
marijuana
270, 269, 265, 263
Maryland, University of
285
maternal-fetal transmission
280
McCormack, Thomas P.
276
MDC (macrophage derived chemokine)
285
MDMA overdose
265
Medicaid
276, 270, 269
medical information online
275
medical research organization
278
Medicare Parts A and B
276
Miami
270
Mirken, Bruce
270
monoclonal antibodies
284
Montreal
270
most favored customer
280
MRSA
281
mutations
283
NAC
268, 266
needle exchange
280, 278
nelfinavir
271, 269, 267, 265, 263
nelfinavir+AZT+3TC
269
neuropathy
265
nevirapine
280, 271, 269
New York City
270, 265
news online
271
nitrite inhalants
280
Nolan, Garry
279
non-Hodgkin's lymphoma
284
nutrition
268, 265, 264
off-label promotion
284
opportunistic infections
264
partisanship
276
patient assistance programs
265
pediatric
275, 274, 267, 263
per capita caps
270
Petrelis, Michael
282
pharmaceutical-company support
281
phenotypic tests
283
PMPA
269
polls
265
poppers
280
pregnancy
280
press
262
PREVEON
285
Principles of Therapy, HIV
274
prisoners
278
progression
264
protease inhibitors
284, 282, 281, 273, 265, 264
protease inhibitors side effects
277
public opinion
265
Qigong
282
quality of care
280, 278
Republicans
276
resistance
283, 274
Retroviruses conference (1997)
265, 264, 263, 262
Retroviruses conference (1998)
284, 278
returning to work
276
ritonavir
269, 267, 265
ritonavir interactions
265
Rituxan(TM)
284
rituximab
284
Ryan White CARE Act
276
Saag, Dr. Michael
279
Saba, Dr. Joseph
283
San Diego
270
San Francisco
270, 265
San Francisco AIDS Foundation
282
San Francisco Bay Guardian
281
saquinavir
283, 274, 269, 268
Scondras, David
267
second generation protease inhibitors
265
service
267
side effects
264
Smith, Denny
269, 264
Social Security
276
SPV-30
267
SSDI
276
SSI
276
standards of care
274
Stanford
266
strains of HIV
282
strategies, treatment
281
surrogate markers
284, 271, 270, 267
survival
276, 274, 266
SUSTIVA(TM)
see: efavirenz
T-20
282, 279
TAG (Treatment Action Group)
264
tape recordings available
279
tat
285
Taxol
277
Tobias, Tadd
275, 271, 269
Toronto
270
travel, hotel arrangements
283
treatment access
268
treatment directories
268
treatment failure
282, 281, 278
treatment guidelines
274
treatment rejectionists
278, 267
treatment strategies
281
triglycerides
277
U.S. Supreme Court
274
UNAIDS
283
United Against AIDS International
280
University of California
275, 267
vaccination
285, 284
vaccine
280, 270
Venezuela
280
vesicular stomatitus virus
279
viral load
282, 273, 271, 270, 265
viral load measurement
279
viral resistance
283, 282
vitamin B-12
264
Walker, Dr. Bruce
284
Washington
270
WASHINGTON POST
275
wasting
281
water quality
266
WORLD newsletter
276
World Wide Web
284
ISSN # 1052-4207
Copyright 1997 by John S. James. Permission granted for noncommercial reproduction, provided that our address
and phone number are included if more than short quotations are used.
This article was provided by AIDS Treatment News. It is a part of the publication AIDS Treatment News.
