Essay/Term paper: Azt

Essay, term paper, research paper:  Medicine

AZT


The AIDS virus is one of the most deadly and most wide spread diseases
in the modern era. The disease was first found in 1981 as doctors around the
United States began to report groups of young, homosexual men developing a rare
pneumonia caused by an organism called Penumocystis carini. These patients then
went on to develop many other new and rare complications that had previously
been seen only in patients with severely damaged immune systems. The Center for
Disease Control in the United States named this new epidemic the acquired
immunodeficiency syndrome and defined it by a specific set of symptoms. In 1983,
researchers finally identified the virus that caused AIDS. They named the virus
the human immunodeficiency virus, or HIV. AIDS causes the immune system of the
infected patient to become much less efficient until it stops working altogether.


The first drug that was approved by the American Food and Drug
administration for use in treating the AIDS virus is called AZT, which stands
for azido-thymidine. AZT was released under the brand name of Retrovir and it's
chemical name is Zidovudine, or ZDV. The structural name of AZT is 3'-azido-3'-
deoxythymidine. AZT works by inhibiting the process of copying DNA in cells.
More specifically, AZT, inhibits the reverse transcriptase enzyme, which is
involved in the DNA replication process. When DNA is replicating in a cell,
there is a specific enzyme that works along one side of the original DNA strand
as the DNA is split into two strands, copying each individual nucleotide. This
enzyme is only able to work in one direction along the nucleotide string,
therefore a different enzyme, or rather a series of different enzymes is
required to work in the opposite direction. Reverse transcriptase is one of the
enzymes that is required to work in the opposite direction. AZT works by bonding
to the reverse transcriptase enzyme, thereby making it unable to bond with the
nucleotide string and making it unable to fulfill it's role. This whole process
is used by the HIV virus to replicate itself so that it can continue to infect
more cells.

AZT was originally developed over 20 years ago for the treatment of
lukemia. The concept behind this was that the AZT was supposed to terminate the
DNA synthesis in the growing lukemia lymphocytes, thereby stopping the disease.
AZT was rejected at this point because it failed to lengthen the lives of test
animals.

The problem with the AZT drug is that it is not perfect. First of all,
AZT will not bond to each and every reverse transcriptase enzyme in the body,
and therefore it cannot shut down the HIV production completely. The reason for
this is because to put enough AZT in the patient to completely shut down the HIV
production would probably kill the patient. The second, and most serious problem
with AZT is that it also goes into normal, healthy cells and will inhibit their
reverse transcriptase enzyme and will therefore inhibit their ability to produce
new, healthy cells. However, AZT does have an ability to specifically target HIV
infected cells to a certain degree so that it does not kill each and every cell
it gets into. However, it does kill a high proportion of the cells that it gets
into, thereby giving it a high toxicity level.

The formula for AZT is C H N O . The molar mass of AZT is 267.24 grams
per mole. AZT's melting point is between 106 C and 112 C. AZT is soluble in
water, which is important so that it may dissolve into the human blood and be
distributed to the cells. AZT is usually taken in a pill format, but it is
absorbed by the skin, which can make it dangerous for people handling the drug.

There is quite a bit of controversy about the effectiveness of AZT. Most
experts agree that AZT delays the progression of HIV disease; the drug may also
prolong the disease-free survival period. However, many doctors still disagree
with using AZT as a treatment for AIDS. Peter Duesberg, a professor of molecular
biology at the university of California, Berkley, says that "In view of this,
[the cytotoxicity level of AZT] there is no rational explanation of how AZT
could be beneficial to AIDS patients, even if HIV were proven to cause AIDS."
This comment stems from the fact that AZT has a very high cytotoxicity level,
which means that while it kills the infected cells, it will also kill perfectly
healthy cells. According to Dr. Duesberg, AZT will kill approximately nine
hundred and ninety nine healthy cells for each infected cell that it kills. Most
of this opposition to AZT stems from the fact that the initial testing for the
drug had severe problems associated with it. These initial tests were performed
with two groups of AIDS patients. The volunteering patients were secretly
divided into two groups using a double-blind system, where neither the patients
nor the doctors are aware of who is in the placebo, or control group, and who is
in the AZT group. These tests were performed by the FDA at twelve medical
centers throughout the United States. The study actually became unblinded almost
immediately as some patients discovered a difference in taste between the
placebo and AZT caplets and other patients took the capsules to chemists to have
them analyzed. The doctors found out the differences between AZT patients and
the placebo patients by very obvious differences in blood profiles. An FDA
meeting was convened and the decision was made to keep all of the useless data,
and therefore the bad data was thrown in with the good data and it ended up
making all of the data virtually useless. In fact, according to some sources,
AZT ended up shortening the lifespans of many of the patients taking it. AZT is
also thought to be a possible carcinogen, although it has not been around long
enough for any conclusive results to be obtained. After AZT was approved for use,
mortality statistics were taken, they showed a mortality rate of 10% after 17
weeks, with the original number of patients being 4805. The FDA tests, with
their skewed statistics, showed only a 1% mortality rate. AZT also had some
strange side-effects that were reported with it's use, such as raising the IQs
of 21 children who took the drug by 15 points, 5 of the children died.

The newest treatments with AZT are combining AZT with other drugs, such
as ddI. These tests were being performed, once again in the double-blind format,
just like the original FDA tests. Three different groups were tested, ones
taking only AZT, ones taking only ddI and ones taking a combination of both ddI
and AZT. The Data Safety Monitoring Board (DSMB), and organization that monitors
all testing in the United States secretly unblinded the test, as they do with
all double-blind tests, and found that the AZT patients had a much higher
mortality rate than those in the straight ddI and the ddI and AZT tests. The
DSMB found the difference in the tests to be high enough to stop the trials
early.

In August of 1994, the FDA approved AZT for use by pregnant, AIDS
infected women. Once again it was conducted in a double-blind method and was
placebo controlled. The therapy was begun 14-34 weeks after pregnancy. However,
in this testing it was found that in the AZT mothers, the AIDS transmission rate
to the babies was about 8.3% while the placebo group was about 25.5%. Therefore
the AZT was reducing the AIDS transmission by two thirds.

It is still not clear as to the effectiveness of AZT to stop or hinder
the progress of the AIDS virus. Most experts today consider AZT to be a valid
way to treat AIDS and HIV infection, but they are constantly experimenting with
new combinations of different drugs such as ddI and AZT to try to better treat
AIDS patients. The massive administrative errors in the initial testing have set
the AZT research back and have fostered unlooked for antipathy. As the
treatments become more sound and more reliable, AZT will find it's place in AIDS
treatments.

EndNotes

Lauritsen, John. Poison by Prescription - The AZT Story. New York; Asklepios
Publishing, 1990. pg.7.

Lauritsen, John. Poison by Prescription - The AZT Story. New York; Asklepios
Publishing, 1990. pg.7.

Lauritsen, John. Poison by Prescription - The AZT Story. New York; Asklepios
Publishing, 1990. pg.23.

Lauritsen, John. Poison by Prescription - The AZT Story. New York; Asklepios
Publishing, 1990. pg.49.

Whitmore, Arthur. AZT Approved for Preventing Maternal-Fetal HIV
Transmission. Internet: http://www.hivpositive.com/f-DrugAdvisories/II-
FDA/4.htm. August 8, 1994.

Bibliography

Lauritsen, John. Poison by Prescription - The AZT Story. New York: Asklepios
Publishing, 1990.

Pinsky, Laura. Douglas, Paul Harding. Metroka, Craig. The Essential HIV
Treatment Fact Book. New York: Simon & Schuster Inc., 1992.

Kaiser, Jon D. Immune Power - A Comprehensive Treatment Program for HIV. New
York: St.Martin's Press, 1993.

Whitmore, Arthur. AZT Approved For Preventing Maternal-Fetal HIV Transmission.
Internet: http://www.hivpositive.com/f-DrugAdvisories/II-FDA/4.htm,
August 8, 1994.

Whitmore, Arthur. FDA Grants Accelerated Approval For 3TC With AZT To Treat
AIDS. Internet: http://www.hivpositive.com/f-DrugAdvisories/II-FDA/17.htm,
November 20, 1995.

Clark, Martina. AZT: Pediatric Study Changed. Internet:
http://www.out.org/HIV/AZT_pediatric_study_changed.htm, "W.O.R.L.D. - A
Newsletter about Women & HIV" April 22, 1995.