Download What is AZT?

Chapter 10
An Evolving Enemy
• Silvio Penta
• Christie DiDonato
• Carl Tuoni
• Beth Miller
Question
• What is AZT and how does it stop HIV
from reproducing and causing AIDS? In
the early 1990s researchers began to find
AZT -resistant strains of HIV in recently
infected patients who have never been
treated with AZT. How can this be?
Explain
Background
• Azidothymidine, or AZT, was
the first antiretroviral drug
approved for treatment of
HIV. First synthesized in 1964
by the US National Institute of
Health for treatment of
cancer. It was found
ineffective on cancer infected
lab rats and was shelved. In
1985 it was reexamined as an
AIDS treatment and was
found to prolong the life of
AIDs infected patients.
http://www.niaid.nih.gov/publications/hiv
aids/23.htm
http://www.chrisdellavedova.com/wpcontent/uploads/2007/10/scientist.gif
What is AZT?
• AZT is the foundation stone
•
•
•
• AZT works by interfering
of the AIDS drug
with cell division.
construction.
• DNA is a chain of molecular
beads (nucleotides) one
It was the first drug
being Thymidine, of which
approved for the treatment
AZT is a defective analog.
of AIDS and the HIV
This can be threaded on the
infection in 1987.
chain, but stops further
It is usually used in two or
growth through the addition
three drug “cocktails”,
of natural nucleotides.
rather than alone.
• This mechanism stops the
HIV from inserting itself into
It is also the main drug
human DNA.
used to prevent HIV
transmission from mother to
www.3dchem.com
child.
AZT
• AZT is one of the nucleoside reverse transcriptase
inhibitors (NRTIs). These drugs work by disrupting
an HIV protein or enzyme called reverse
transcriptase, which is involved in the production of
new viruses. These drugs block the reverse
transcriptase enzyme.
www.aidsinfonet.org/factsheet_det
ail.php?fsnumber=411
AZT continued…
• AZT does not destroy the
•
HIV infection, but only
delays the progression of
the disease and the
replication of the virus,
even at high doses.
During prolonged AZT
treatment, HIV has the
ability to gain an increased
resistance by mutation of
the reverse transcriptase.
www.aras.ab/articles
AZT resistant strains in
untreated patients?
• Mutations that result in drug-resistant variants
•
can occur both prior to the administration of
antiviral drugs as well as during therapy.
HIV is notorious for its’ ability to develop drug
resistance in patients taking antivirals.
Resistance in AZT is peculiar in that multiple
amino acid changes and mutations build up over
time, yielding a number of virus variants with a
high-level drug resistance.
AZT resistance
• HIV does not make perfect copies of itself. With billions
•
of viruses being made every day, lots of small, random
differences like mistakes can happen. The differences
are called mutations.
Mutations that change the parts of the virus the drugs
are meant to stop can keep the drugs from working.
When the drug no longer works against HIV, it is called
drug resistance. The virus with the mutation is resistant
to the drug.
www.atdn .org/simple/resistance.html
• When AZT resistant strains of
•
•
HIV are produced they keep
multiplying while the non AZT
resistant strains are killed off.
Eventually there are only AZT
resistant strains of HIV left in
the body.
This strain of HIV will then
spread like the normal virus.
Drug-resistant viruses may be
transmitted in primary
infection via sexual or
intravenous routes.
Side Effects of AZT
• AZT has a dark side. Although the immediate results of
•
•
the treatment in AIDS patients may be positive, over
time they produce the same symptoms of AIDS itself!
There are numerous debilitating or even fatal side
effects.
Severe anemia that without transfusions could be
deadly.
Damage to the blood, bone marrow, nerves and muscle
is believed to arise from effects on the mitochondria,
regulating organelles in every cell.
http://aliveandwell
The Links:
http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s11490.htm
http://www.aids.org/atn/a-191-06.html
http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=10220348
5.html
May There Be a Cure