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.