AZTAZTwide spread diseasesin the modern era.
The disease was first found in 1981 as doctors around theUnited States began to report groups of young, homosexual men developing a rarepneumonia caused by an organism called Penumocystis carini. These patients thenwent on to develop many other new and rare complications that had previouslybeen seen only in patients with severely damaged immune systems. The Center forDisease Control in the United States named this new epidemic the acquiredimmunodeficiency syndrome and defined it by a specific set of symptoms. In 1983,researchers finally identified the virus that caused AIDS.
They named the virusthe human immunodeficiency virus, or HIV. AIDS causes the immune system of theinfected patient to become much less efficient until it stops working altogether. The first drug that was approved by the American Food and Drugadministration for use in treating the AIDS virus is called AZT, which standsfor azido-thymidine. AZT was released under the brand name of Retrovir and it’schemical 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 isinvolved 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 strandas the DNA is split into two strands, copying each individual nucleotide. Thisenzyme is only able to work in one direction along the nucleotide string,therefore a different enzyme, or rather a series of different enzymes isrequired to work in the opposite direction. Reverse transcriptase is one of theenzymes that is required to work in the opposite direction. AZT works by bondingto the reverse transcriptase enzyme, thereby making it unable to bond with thenucleotide string and making it unable to fulfill it’s role. This whole processis used by the HIV virus to replicate itself so that it can continue to infectmore cells.
AZT was originally developed over 20 years ago for the treatment oflukemia. The concept behind this was that the AZT was supposed to terminate theDNA synthesis in the growing lukemia lymphocytes, thereby stopping the disease. AZT was rejected at this point because it failed to lengthen the lives of testanimals. 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 forthis is because to put enough AZT in the patient to completely shut down the HIVproduction would probably kill the patient.
The second, and most serious problemwith AZT is that it also goes into normal, healthy cells and will inhibit theirreverse transcriptase enzyme and will therefore inhibit their ability to producenew, healthy cells. However, AZT does have an ability to specifically target HIVinfected cells to a certain degree so that it does not kill each and every cellit gets into. However, it does kill a high proportion of the cells that it getsinto, thereby giving it a high toxicity level. The formula for AZT is C H N O .
The molar mass of AZT is 267. 24 gramsper mole. AZT’s melting point is between 106 C and 112 C. AZT is soluble inwater, which is important so that it may dissolve into the human blood and bedistributed to the cells. AZT is usually taken in a pill format, but it isabsorbed 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.
Mostexperts agree that AZT delays the progression of HIV disease; the drug may alsoprolong the disease-free survival period. However, many doctors still disagreewith using AZT as a treatment for AIDS. Peter Duesberg, a professor of molecularbiology at the university of California, Berkley, says that “In view of this,the cytotoxicity level of AZT there is no rational explanation of how AZTcould 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 perfectlyhealthy cells.
According to Dr. Duesberg, AZT will kill approximately ninehundred and ninety nine healthy cells for each infected cell that it kills. Mostof this opposition to AZT stems from the fact that the initial testing for thedrug had severe problems associated with it. These initial tests were performedwith two groups of AIDS patients. The volunteering patients were secretlydivided into two groups using a double-blind system, where neither the patientsnor the doctors are aware of who is in the placebo, or control group, and who isin the AZT group.
These tests were performed by the FDA at twelve medicalcenters throughout the United States. The study actually became unblinded almostimmediately as some patients discovered a difference in taste between theplacebo and AZT caplets and other patients took the capsules to chemists to havethem analyzed. The doctors found out the differences between AZT patients andthe placebo patients by very obvious differences in blood profiles. An FDAmeeting 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 upmaking 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 isalso thought to be a possible carcinogen, although it has not been around longenough 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 17weeks, with the original number of patients being 4805. The FDA tests, withtheir skewed statistics, showed only a 1% mortality rate. AZT also had somestrange side-effects that were reported with it’s use, such as raising the IQsof 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, suchas ddI. These tests were being performed, once again in the double-blind format,just like the original FDA tests.
Three different groups were tested, onestaking only AZT, ones taking only ddI and ones taking a combination of both ddIand AZT. The Data Safety Monitoring Board (DSMB), and organization that monitorsall testing in the United States secretly unblinded the test, as they do withall double-blind tests, and found that the AZT patients had a much highermortality rate than those in the straight ddI and the ddI and AZT tests. TheDSMB found the difference in the tests to be high enough to stop the trialsearly. In August of 1994, the FDA approved AZT for use by pregnant, AIDSinfected women.
Once again it was conducted in a double-blind method and wasplacebo 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 rateto the babies was about 8. 3% while the placebo group was about 25. 5%.
Thereforethe AZT was reducing the AIDS transmission by two thirds. It is still not clear as to the effectiveness of AZT to stop or hinderthe progress of the AIDS virus. Most experts today consider AZT to be a validway to treat AIDS and HIV infection, but they are constantly experimenting withnew combinations of different drugs such as ddI and AZT to try to better treatAIDS patients. The massive administrative errors in the initial testing have setthe AZT research back and have fostered unlooked for antipathy.
As thetreatments become more sound and more reliable, AZT will find it’s place in AIDStreatments. EndNotesLauritsen, John. Poison by Prescription – The AZT Story. New York; AsklepiosPublishing, 1990.
pg. 7. Lauritsen, John. Poison by Prescription – The AZT Story. New York; AsklepiosPublishing, 1990.
pg. 7. Lauritsen, John. Poison by Prescription – The AZT Story.
New York; AsklepiosPublishing, 1990. pg. 23. Lauritsen, John. Poison by Prescription – The AZT Story.
New York; AsklepiosPublishing, 1990. pg. 49. Whitmore, Arthur. AZT Approved for Preventing Maternal-Fetal HIVTransmission.
Internet: http://www. hivpositive. com/f-DrugAdvisories/II-FDA/4. htm. August 8, 1994.
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