HIV is a deadly and dangerous
virus for several reasons. Recent research using mathematical models
predicts that the rate of virus production during active infection
is approximately 10.3 x 109 virions per day. Additionaly, the infected
cells have a life span that averages 2.2 days (Schwartz and Nair,
1999). Moreover, HIV reverse transcriptase has a high rate of mutation
in the DNA copies. Consequently, these traits of HIV produce a virus
that is constantly changing and avoiding an adaptive immune response
(www.aegis.com/)
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Reverse Transcriptase Inhibitors |
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Inhibitors of reverse transcriptase
have been vital in the treatment of HIV. Reverse transcriptase inhibitors
prevent viral reverse transcriptase from synthesizing and incorporating
the viral RNA into the genomic DNA (www.aegis.com).
Reverse transcriptase has been particularly effective because there
is little interference with the synthesis of cellular DNA (Schwartz
and Nair, 1999).
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This
animation shows reverse transcriptase inhibitingthe synthesis of viral
RNA into DNA, thereby preventing the virus from incorporating HIV
DNA into the healthy genome. Used with permission from Cells
Alive. |
Perhaps the most popular
reverse transcriptase inhibitor is ZDV (Retrovir), formerly known
as AZT (Azido-thymidine). This drug is a thymidine analog and a
natural precursor to DNA. Other popular reverse transcriptase inhibitors
include didanosine (Videx), lamivudine (Epivir), stavudine (Zerit),
and zacitabine (HIVID) (Carpenter et al., 1996).
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Protease inhibitors are another
example of common antiretroviral drug therapy. As discussed previously,
HIV uses the host cell to synthesize new HIV virions. Protease inhibitors
block critical steps of post translational virion assembly which
depend on proteolytic cleavage for activation (www.aegis.com/topics/basics/hivandaids.html).
A common target of protease inhibitors is the envelope protein gp160,
which must be fragmented into gp120 and gp41 in order to produce
functional HIV. The popular protease inhibitors include indinavir
(Crixivan), ritonavir (Norvir), nelfinavir (viracept), and saquinavir
(Fortovase and Invirase) (Schwartz and Nair, 1999).
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Treatment of HIV with monotherapy
(one drug) in not effective due to the rapid mutation and proliferation
of HIV (Schwartz and Nair, 1999). The most recent research in this
field has suggested that multidrug therapy targeting HIV reverse
transcriptase and proteases is the most effective treatment. However,
taking a reverse transcriptase inhibitor and protease inhibitor
does not ensure an immune recovery from HIV. The drugs for each
category must be changed frequently in order to avoid HIV immunity
to the drugs (Stine, 1999).
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