Untitled Essay, Research Paper

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.