HIghly Active Anti-retroviral
therapy (HAART) has revolutionised HIV treatment,
bringing hope to millions of sufferers. It has resulted
in a profound decline in the number of deaths due
to AIDS in the Western World. In USA in recent years
the number of AIDS deaths has decreased by 70%.
The benefits of HAART have been linked with
decreased rates of AIDS opportunistic infections,
improved quality of life and increased survival.
There are three main classes
of drugs:
Protease
Inhibitors (PI)
Non-Nucleoside
Reverse Transcriptase Inhibitors (NNRTI)
Nucleoside Reverse
Transcriptase Inhibitors (NRTI)
They mainly work by affecting the action of key enzymes the
HIV virus needs to reproduce, thereby preventing HIV
from multiplying. They are used in what is called
combination therapy; therapeutic guidelines recommend
combinations of three or four anti-HIV drugs as treatment
for HIV. Prescribed combinations of the different
drugs taken regularly usually leads to a profound
decrease in HIV viral load and a substantial increase
in CD4 T-cell count.
N.B.
The information listed here is based on anti-HIV drug
use in the developed world, and may not translate
to African environments. It is only intended as a
guide to the therapeutic use of the different drugs.
Anti-retrovoral therapy is not a cure for HIV/AIDS.
Protease
Inhibitors
Protease inhibitor drugs work by blocking a key protease enzyme
that HIV needs to reproduce. This results in defective
HIV particles that are unable to infect new cells.
Protease Inhibitors are used in combination therapy
with other anti-HIV drugs.
|
Name
|
Generic name
|
Other name
|
Manufacturer
|
Approval date
|
|
Agenerase
|
amprenavir
|
|
Glaxo Wellcome
|
15 April 99
|
|
Crixivan
|
indinavir
|
|
Merck & Co., Inc.
|
13 March 96
|
|
Fortovase
|
saquinavir
|
soft-gel cap
|
Hoffmann-La Roche
|
07 November 97
|
|
Invirase
|
saquinavir
|
hard-gel cap
|
Hoffmann-La Roche
|
06 December 95
|
|
Kaletra
|
lopinavir/ritonavir
|
|
Abbott Laboratories
|
15 September 00
|
|
Norvir
|
ritonavir
|
|
Abbott Laboratories
|
01 March 96
|
|
Viracept
|
nelfinavir
|
|
Agouron Pharmaceuticals
|
14 March 97
|
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Non
Nucleoside Reverse Transcriptase Inhibitors
NNRTI drugs work by blocking the
action of the reverse transcriptase enzyme of HIV.
This effect renders the virus unable to transcribe
its genes into a form that would allow them to be
incorporated into the human genes. NNRTI have no action
on cells already infected with HIV. This is also the
case with NRTI (nucleoside reverse transcriptase inhibitor)
drugs, but the mechanism of the NNRTI and NRTI anti-HIV
drugs are different.
|
Name
|
Generic name
|
Other name
|
Manufacturer
|
Approval date
|
|
Rescriptor
|
delavirdine
|
|
Pharmacia & Upjohn
|
04 April 97
|
|
Sustiva
|
efavirenz
|
|
DuPont Pharmaceuticals
|
17 September 98
|
|
Viramune
|
nevirapine
|
|
Boehringer Ingelheim
Pharmaceuticals Inc.
|
21 June 96
|
Top
Nucleoside
Reverse Transcriptase Inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
work by terminating the growing DNA (gene) chain of
HIV as it is trying to reproduce itself. NRTI drugs
obstruct the building blocks of genetic material (RNA
or DNA) from being assembled together. NRTI’s block
a crucial step in HIV’s life cycle where the reverse
transcriptase enzyme changes the HIV genetic material
(RNA) into the form of DNA that can be incorporated
into an infected cell’s own DNA. This results in defective
HIV particles that are unable to infect new cells,
and prevents the virus from multiplying.
|
Name
|
Generic name
|
Other name
|
Manufacturer
|
Approval date
|
|
Combivir
|
zidovudine / lamivudine
|
|
Glaxo Wellcome
|
26 September 97
|
|
Epivir
|
lamivudine
|
3TC
|
Glaxo Wellcome
|
17 November 95
|
|
Hivid
|
zalcitabine
|
ddC
|
Hoffmann-La Roche
|
19 June 92
|
|
Retrovir *
|
zidovudine
|
AZT
|
Glaxo Wellcome
|
19 March 87
|
|
Videx
|
didanosine
|
ddI
|
Bristol Myers-Squibb
|
09 October 91
|
|
Zerit
|
stavudine
|
d4T
|
Bristol Myers-Squibb
|
24 June 94
|
|
Ziagen
|
abacavir
|
|
Glaxo Wellcome
|
17 December 98
|
* Refers to capsules. Retrovir syrup approved 28th
Sept 1989, Retrovir injection 2nd Feb 1990
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Combination
therapy / treatment options
Therapeutic guidelines recommend combinations of three or four
anti-HIV drugs as treatment for HIV. Given the quantity
of different drugs available on the market, the number
of possible different combinations is huge and potentially
very confusing. Nonetheless there are some treatment
options that are more commonly used and generally
recommended. These are:
1.
Protease Inhibitor with 1-3 nucleoside
reverse transcriptase inhibitor (NRTI) drugs -
(PI + NRTI + NRTI)
2.
Double Protease Inhibitor combinations
with 2 NRTI or a an NRTI + nNRTI- (PI
+ PI) + 2NRTI or nNRTI
3.
Protease Inhibitor with 2 NRTI drugs
and a non-nucleoside reverse transcriptase inhibitor
(nNRTI)
(PI + nNRTI +NRTI
+ NRTI)
Even within each treatment
option there are numerous different treatment options
and combinations. Some may be affected by drug interactions
between certain kinds of HIV drugs that may be beneficial
or harmful and others have just not been tested yet.
The efficacy and outcomes of the various combinations
are also affected by the patient’s treatment history,
e.g. whether they are HIV drug naïve (first time user), if they have a history of
developing resistance to a particular drug or drug type
etc.
To have a better idea about
how the drugs are used see treatment guidelines for
the individual drugs.
DO NOT USE THIS INFORMATION AS YOUR SOLE GUIDE
TO HIV TREATMENT. The state-of-the-art
of HIV treatment is a rapidly changing field. Consult a doctor or physician who is HIV-AIDS knowledgeable, whenever possible. It is important
to keep up with field or your health may suffer the
consequences. Not all Doctors have the time to do
this.
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Dosage
See the HAART page for standard dosages.
For other dosage regimens read information on the
individual drug.
Because
the drugs are taken in combinations of the different
types hence the name "Combination Therapy",
the total number of pills and capsules that have to
be swallowed in a day can be quite large. The number
ranges from an almost reasonable 10 pills to 24 or
more.
Patient
psychology:
The
patient's willingness to stick rigidly to the therapeutic
regimen will be just as important as the effectiveness
of the drugs they will be taking. .Remember
HIV drugs have to be taken for the rest of the patients
life. They must be taken at regular intervals to keep
drug concentrations in the blood at high enough levels
to prevent the development of resistance. And the
drugs have unpleasant side effects. All patient's
must be given as much information and support as possible.
Encouraging the development of patient support groups
will help a great deal.
Cost
of treatment
The high cost of HIV drugs has been very
much in the news with drug companies after coming
under great pressure finally agreeing to sell drugs
in Africa at discounted prices or at cost. So just
how much will they cost? Which treatment option is
the cheapest? It is for sure cost is going to be the
major determinant of which treatment protocols will
be made available to HIV sufferers in Africa.
Not surprisingly the cheapest treatment
option is Treatrment Option 1, but the price varies
greatly, depending on what drugs are used. The cheapest
combination is Viramune / Epivir / Zerit at $606 per
year.
Other combinations are considerably more
expensive because even at so called discount prices,
the yearly cost is still considerable at $1,000 plus,
andsome drugs are not even offered at discounts. It is certain that many new different
treatment options with unknown outcomes will be tried
out as cost becomes a driving factor.
To see the price of some of of the most common treatment
combinations follow these links Option1,
Option2,
Option3.
Resistance
and Cross-Resistance
HIV drug resistance occurs when HIV replicates in
the presence of antiretroviral drugs. This happens
when the HIV viral load (RNA) levels are not undetectable
despite antiretroviral drug and means HIV has found
a way to grow even with adequate drug levels present.
This happens when the HIV viral load (RNA) levels
rebound or do not decrease even in the presence of
adequate drug levels in the blood.
Resistance can also occur when there are
insufficient antiretroviral levels in the blood due
to inadequate drug dosing, if there is impaired drug
absorption, increased drug metabolism or not taking
the anti-retrovirals exactly as directed due to poor
patient compliance. Resistance to one drug in a class
may affect all the drugs in that class and this is
called cross-resistance.
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Side
Effects
HIV anti-retroviral drugs are powerful substances
and all have side effects that result from their use.
The side effects range from irritating to unpleasant
or potentially life threatening and fatal. Many of
the side effects are quite unpleasant and may lead
to patient’s not adhering to prescribed treatment
guidelines. It is important that patients are made
aware of the possible side effects so that they not
only know what to expect, but also so that they can
make their doctor aware of the onset of possibly dangerous
side effects.
Special
populations
Pregnant women and children
– there are special guidelines for using drugs in this
group of people. Consult your doctor or a website that
has information regarding the use of HIV drugs.
Last
Updated:
November 19, 2002
AIDS
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