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Monday, June 29, 1987 dw ;1 ,Ai ji ulBflo
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Scientists test wide range of medical strategies
for waging war against insidious AIDS virusHalf a decade of intense research on AIDS has pro-
duced only one approved medicine for its victims:
the drug known as AZT.
AZT is not a cure. It simply reduces the severity of
some AIDS symptoms in some AIDS patients, pro-
longing life but not preventing death.
It triggers serious side effects; AZT recipients suf-
fer from severe headaches and many have to un-
dergo blood transfusions for anemia.But AZT is just the first of the many scientific
weapons that will ultimately battle the AIDS virus.
Drug companies are studying numerous chemical
compounds, trying to find a substance that coun-
teracts AIDS the most effectively with the fewest det-
rimental side effects. Biomedical researchers
around the globe are investigating several strate-
gies for producing a vaccine that would immunize
potential AIDS victims against infection.Chemists have already provided useful tests for
antibodies to the AIDS virus, aiding in diagnosis and
helping to keep the nation's blood supplies safe.
But for now, medical methods of attacking the
AIDS epidemic are limited. Education is the most ef-
fective way of slowing the spread of AIDS. People
who change their behaviors to conform with AIDS
prevention guidelines run very little risk of en-
countering the deadly virus.TREATMENTS FOR AIDS
A DRUG THAT FIGHTS AIDS
Enzyme translates code in RNA into DNA
AIDS
vrus/ AZT interrupts
formation of DNA
DNA Cl
RNACe
AIDS virus
enters;cell Proteins
Cell nucleus
Meesenger RNA ( 2
New AIDS virus particles
AZT, or azidothymidine, was licensed for use to treat AIDS vic-
tims in March. It is now technically known as zidovudine and mar-
keted under the trade name Retrovir.
It does not cure AIDS, and it has several serious side effects,
including anemia, fever, nausea and severe headaches.
But tests show it can reduce the severity of symptoms and pro-
long the lives of some AIDS victims, especially those who have con-
tracted Pneumocystis caring, an ordinarily rare form of pneumonia
that strikes many AIDS patients.
Experts believe that AZT retards the reproduction of the AIDS
virus within infected cells. When a cell is invaded, an enzyme and
RNA from the virus begin to create new genetic material made of
DNA. The DNA can mingle with the genes of the host cell in the
cell's nucleus. At some later time the viral DNA may produce new
copies of the virus, killing the host cell.
AZT's chemical structure allows it to masquerade as a sub-
stance ordinarily used by the enzyme in making DNA. When the
enzyme tries to use the AZT, the process is blocked, preventing the
viral DNA from being manufactured. Thus AZT treatments slow
down the progression of AIDS by preventing the virus from taking
over as many cells as it would if unchecked.
Researchers want to find out if AZT might prevent the disease
from developing in the first place. Plans have been made at four
U.S. medical centers to give AZT to people who have been infected
with the AIDS virus but who have not yet shown symptoms of AIDS.
AZT has so far been used only on sick patients.Only one drug, AZT, has been
licensed in the United States as a
treatment for AIDS. But research-
ers are investigating several other
substances in an effort to find a
way to reverse the symptoms of
AIDS without unacceptable side ef-
fects. Among the substances being
studied:
AL 721
A fat mixture that interferes with
HIV's ability to infect, possibly by
disrupting the virus's membrane.
No adverse effects were observed
during a six-week clinical trial.
ALPHA INTERFERON
A glycoprotein produced by cells
responding to a virus infection. It is
believed to amplify and regulate
immune responses. In AIDS, it is
most promising against Kaposi's
sarcoma. Kaposi's sarcoma has
gone into remission in about 30
percent of treated AIDS patients.
ANTI-HUMAN
ALPHA-INTERFERON
ANTIBODIES
An approach devised by research-
ers who believe alpha interferon re-
leases signals that turn off the im-
mune system in infected people, in-
stead of bolstering it. The four
AIDS patients who participated in
the study of toxicity reportedly ex-
perienced no adverse side effects
Dideoxycytidine NH2
N,
HOCH2 0 N
20NFoscarnet
O 0
NaO P-C ONa
ONa
and were able to return to work. An
effectiveness study is waiting ap-
proval from the Food and Drug Ad-
ministration.
AMPLIGEN
A drug shown to suppress the
AIDS virus in a pilot study of 10 pa-
tients. It also seemed to improve
the immune response. A larger
study of 200 people with ARC is
under way. Ampligen is a synthetic
biological stimulant that behaves
like an artificial virus. It induces the
body to produce interferon. No
toxic side effects were noted in
tests of cancer patients.
DDC
Technically, dideoxycytidine, a
drug similar to AZT. First syn-
thesized in the 1960s in Michigan
as a potential anti-cancer treat-
ment but found to be ineffective.
Laboratory and animal studies
have shown DDC to be more effec-
tive and less toxic than AZT. Side
effects include skin rash, mouth
ulcers, and temporary suppression
of production of blood-clotting
cells called platelets. It has been
given high priority by the National
Cancer Institute, and expanded
human trials are about to begin.
D-PENICILLAMINE
In one trial of 13 AIDS patients at
George Washington UniversityMedical Center it inhibited HIV
reproduction, but also depressed T
cell levels. Researchers now look-
ing for a way to maintain the anti-
viral activity without affecting T
cells.
FOSCARNET
A drug developed in Sweden that
has been used to treat cytome-
galovirus in patients with weak-
ened immune systems. It also has
been used to treat herpes. It inhib-
its reverse transcriptase. The Na-
tional Institute for Allergies and In-
fectious Diseases is planning a
study of anti-viral activity in AIDS
patients.
HPA-23
The drug used in Paris to treat ac-
tor Rock Hudson before his death.
It inhibits reverse transcriptase in
several retroviruses in the labora-
tory. The main adverse side effect
in trials for safety and tolerance
was a drop in platelets count. A
study is planned to determine the
optimal dosage.
IMREG-1
A patented substance derived from
white blood cells that boosts the
immune system. More than 100
AIDS and ARC patients have been
treated in effectiveness trials. A re-
duction In the rate of destruction of
T4 cells was shown in some pa-
D-Penicillamine
SH NH2
I I
(CH3)2C CHCOOHO Ribavirin
H2N N
N
N
HOCH2
O
HO OH
tients; an increase in the number of
cells was reported In others. Now
in the final stage of testing before
the manufacturer applies to the
Food and Drug Administration for
permission to market.
ISOPRINOSINE
A drug originally developed to en-
hance memory in the elderly. In two
studies, it was found to improve
immune function in ARC patients.
Late last year, a study began that
eventually will involve 2,000 HIV-in-
fected people in the United States,
Scandinavia and Australia.
PEPTIDE T
A peptide that has inhibited the
AIDS virus in laboratory experi-
ments. It has shown no toxic side
effects. Peptide T mimics the
molecule on the AIDS virus coat
that attaches itself to T4 cells. By
blocking the attachment site, Pep-
tide T could protect T4 cells from
the virus. The first U.S. human tri-
als are about to begin; a Swedish
group recently started a control
trial with 36 AIDS patients.
RIBAVIRIN
Synthetic drug used to treat a viral
respiratory infection in children. It
failed to prove effective in a follow-
up study on patients with chronic
swollen glands after originally en-
couraging reports.TESTING FOR AIDS
Since testing blood for the AIDS virus itself is
difficult and costly, mass screening uses a test
that finds antibodies to the AIDS virus.
In the ELISA test, the simplest and cheapest
method, a blood sample is added to bits of
proteins from AIDS virus grown in the laboratory.Lab-grown
HIV virusIf the blood contains antibodies, they will attach
to the virus particles. Chemical reactions will then
change the color of the mix.
The test often indicates the presence of anti-
bodies when none are actually there. So another
test is used to confirm results from ELISA.
- Antibodies
Positive test
HIV antibodies bind
to viral proteinsPREVENTING AIDS
AIDS, once contracted, is a deadly disease.
But individuals can take steps to prevent infec-
tion. U.S. Surgeon General C. Everett Koop gives
the following advice on how to prevent the spread
of AIDS.
"Knowing the
facts about AIDS
can prevent the
spread of the dis-
ease. Education of
those who risk in-
' fecting themselves
or infecting other
people is the only
way we can stop the
spread of AIDS....
"Although the
SAIDSvirus is found
ii dvnrai uy fil-C. Everett Koop
in severalsbon ay -
quires the virus during sexual contact with an in-
fected person's blood or semen and possibly vag-
inal secretions. The virus then enters a person's
blood stream through their rectum, vagina or
penis....
"Couples who maintain mutually faithful
monogamous relationships (only one continuing
sexual partner) are protected from AIDS through
sexual transmission. If you have been faithful for
at least five years and your partner has been
faithful too, neither of you is at risk. If you have
not been faithful, then you and your partner are at
risk. If your partner has not been faithful, then
your partner is at risk, which also puts you at risk.
This is true for both heterosexual and homosex-
ual couples.
"Unless it is possible to know with absolute
certainty that neither you nor your sexual partner
Is carrying the virus of AIDS, you must use pro-
tective behavior. Absolute certainty means not
only that you and your partner have maintained a
mutually faithful monogamous sexual relation-
ship, but it means that neither you nor your part-'
ner has used illegal intravenous drugs.
"Some personal measures are adequate to
safely protect yourself and others from infection
by the AIDS virus and its complications."Among these are:
"If you have been involved in any of the
high- risk sexual activities described above or
have injected illicit Intravenous drugs into your
body, you should have a blood test to see if you
have been infected with the AIDS virus.
"If your test is positive or if you engage in
high risk activities and choose not to have a test,
you should tell your sexual partner. If you jointly
decide to have sex, you must protect your partner
by always using a rubber (condom) during (start
to finish) sexual intercourse (vagina or rectum).
"If your partner has a positive blood test
showing that he-she has been infected with the
AIDS virus or you suspect that he-she has been
exposed by previous heterosexual or homosexual
behavior or use of intravenous drugs with shared
needles and syringes, a rubber (condom) should
always be used during (start to finish) sexual in-
tercourse (vagina or rectum).
r "If you or yourpartner is at high risk, avoid
mouth contact with the penis, vagina, or rectum.
"Avoid all sexual activities which could
cause cuts or tears in the linings of the rectum,
vagina, or penis....
, "Do not have sex with prostitutes. Infected
male and female prostitutes are frequently also
intravenous drug abusers; therefore, they may in-
fect clients by sexual intercourse and other intra-
venous drug abusers by sharing their intravenous
drug equipment. Female prostitutes also can in-
fect their unborn babies....
"No one should shoot up drugs because ad-
diction, poor health, family disruption, emotional
disturbances and death could follow. However,
many drug users are addicted to drugs and for
one reason or another have not changed their be-
havior. For these people, the only way not to get
AIDS is to use a clean, previously unused needle,
syringe or any other implement necessary for the
injection of the drug solution. ...
"Persons who have engaged in homosexual
activities or have shot street drugs within the last
10 years should never donate blood."
From Surgeon General's Report on Acquired immune
Deficiency Syndrome, U.S. Department of Health and Human
Services, 1987SEEKING AN AIDS VACCINE
The main approach to producing an AIDS vac-
cine has been finding a protein that will cause the
body's Immune system to produce antibodies to
the AIDS virus.
With some ordinary vaccines, killed vaccine
particles are used to induce antibody formation.
With others, a strain of the virus that does not
cause the disease is used. Such strategies are
unlikely to be used with AIDS, because it would
be hard to know for sure that any strain would not
cause the disease, and for fear that a live virus
might sneak in among the dead ones.
A vaccine using real virus particles, whether
alive or killed, is unlikely for AIDS. Even a variant
virus that doesn't cause AIDS would be risky, be-
cause it might mutate in the body into the deadly
form. And scientists fear that genetic material
from viruses might cause cancer later in those
receiving the vaccine.
One group of researchers produced a varia-
tion of the AIDS virus that would not invade and
kill cells. But when the mutant virus was put into
human cells in the laboratory, some of the virus
particles changed back into the deadly form.
Researchers have therefore preferred the
strategy of using fragments of the virus in a vac-
cine, such as portions of the virus's outer protein
envelope, or coat.
Using proteins from the virus's coat poses a
problem, though. Many strains of the virus exist,
each with slight differences in the structure of theGENETIC STRATEGIES
Gene splicing methods have also been used to
make experimental vaccines. French researcher
Daniel Zagury has tested a vaccine made by
genetically combining a gene from the AIDS vac-
cine with the harmless virus used in smallpox vac-
cinations.
Zagury injected himself and 11 volunteers with
the vaccine, which caused no ill side effects. The
inoculation induced production of antibodies, but
it isn't known whether such antibodies would pro-
tect against the virus. Similar vaccine tests in
chimpanzees have also produced antibodies, but
those antibodies did not prevent infection when
the chimps were exposed to the AIDS virus.
Since the AIDS virus can enter the body hid-
den within an infected cell, it might escape detec-GENE THERAPY TO FIGHT AIDS
Virus
RNA
CellNew gene
AIDS virus
Core
protein
RNA
Outer
Inner coat
shoein Reverse
protein transcriptase
outer protein. A vaccine based on one virus might
not protect against other strains. Certain parts of
the outer coat seem to remain constant in all
strains, though. A vaccine that would generate
antibodies tuned to this constant portion might
be effective.
Another possibility is designing a vaccine
based on proteins making up the inner shell of
the virus, which doesn't vary as much as the outer
coat.tion by antibodies. Some researchers are seeking
ways to vaccinate people after they have been
infected in an attempt to stop the virus before it
causes AIDS.
One such approach envisions the use of gene
therapy to give an infected cell a new gene that
would produce RNA that matched perfectly with
the virus's RNA, like a hand in a glove. The new
RNA would bind with the virus's RNA, preventing
the virus from reproducing.
Another genetic strategy would be to remove
key genes from the core of the virus and then use
the remaining virus for a vaccine. A virus without
the gene that directs it to multiply might induce
antibody production but would not be able to
reproduce and damage the body's cells.RNA produced
by new geneNew RNA locks
up virus's RNAAZT is the only medicine
licensed to treat AIDS.----
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The Dallas Morning News. [Newspaper article: AIDS, The State of the Science], article, June 29, 1987; (https://texashistory.unt.edu/ark:/67531/metadc916045/m1/3/: accessed June 5, 2024), University of North Texas Libraries, The Portal to Texas History, https://texashistory.unt.edu; crediting UNT Libraries Special Collections.