Antiviral Strategies

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Antiviral Strategies
\ Discussion Paper
mune system is overwhelmed by the virus' rapid and constant
activity.
Considering these points, it makes sense to attempt to slow down
or stop the replication of HIV as much and for as long as possible.
A number of drugs have been shown to significantly reduce levels
of virus found in the blood (viral load), and these drugs almost
always cause some rise in CD4+ cell counts (one common measure of immune health) indicating some degree of response in
the immune system. Conversely, antiretroviral drugs that fail to
reduce viral load also generally fail to improve measures of immune health such as CD4+ cell counts. There is a clear relationship between increased levels of HIV found in blood (viral load)
and more advanced disease states and increased risk of disease
progression. As a general rule, the more virus being produced in
the body, the more rapidly disease progresses. Also the less virus
that is produced, the less opportunity it has to change, or "mutate,"
and become more dangerous. Several studies have now shown
that when viral load is reduced and CD4+ cell counts increase for
24 weeks or longer, disease progression and death are delayed.
The challenge for antiretroviral drug developers is to develop therapies that produce a long-lasting reduction in viral load in both
blood and tissue sites in the body where HIV accumulates. Antiviral therapies must do this, however, without causing serious toxicity or interfering excessively with a person's quality of life. Many
researchers believe that unless virus replication can be controlled,
other efforts at rebuilding immune health will ultimately fail.
Although antiretroviral therapies impair HIV's ability to replicate,
they are not a cure since these drugs have not been shown to
totally eradicate the virus from the body. Over time, the virus
mutates or changes itself enough so that it is no longer affected
by these drugs. This process, called viral resistance, is likely to
happen with almost all antiretroviral drugs to some degree. Many
scientists fear that it will not be possible to fully eradicate the
virus from the body, no matter how good the drugs become or
how early treatment is started. It is still clear, however, that suppressing the virus lengthens survival time and it may be possible
with truly effective therapy to live out a normal life span despite
HIV infection.
When S hould dIStart Treat ment?
There is much debate about when to start anti-HIV therapy, which
therapies to start, and in what combinations. Should treatment
be used immediately when people first learn they are infected, or
should it be 'saved' until there are changes in immunologic or
virologic parameters or until symptoms of HIV develop? These
and other questions need to be considered when deciding when
and which combinations to use. When deciding when to start,

switch or change antiviral regimens there are generally three
medical or biological factors to consider:
4 What is happening with the virus (HIV RNA) levels;
6 What is happening with measures of immune health (particularly CD4+ cell counts);
( What is happening clinically (e.g. symptoms of HIV disease
or recurrent health conditions despite treatment).
Using treatment is not just a matter of medical or biological factors. Several additional factors must be considered, including:
A person's readiness and willingness to commit to constant,
long-term use of therapy;
The impact therapy will have on quality of life;
How long therapies can last, and whether or not there will be
new and better drugs to replace them when they eventually fail;
A person's relative risk of disease progression in the short,
medium, and long-term.
There is no single, absolute answer to the question of when to
start antiviral treatment. Some researchers and physicians believe
that everyone who is HIV infected, regardless of viral load, symptoms, or CD4+ counts should be on treatment. Some believe people
should begin therapy when their CD4+ counts fall below 500 or
their viral load exceeds 10,000-20,000 copies of virus. Others believe that only people with symptoms of HIV disease should consider anti-HIV therapy. One note of agreement is that most researchers and physicians believe that the decision to start antiHIV therapy should be guided by looking at clinical health and
measures of both CD4+ cell counts as well as viral load (HIV RNA
levels). Increasingly information suggests that the new viral load
tests (or HIV RNA tests), coupled with CD4+ cell counts, together
provide the most accurate tool to monitor the risk of HIV disease
progression. The most commonly used viral load tests are Roche's
PCR (polymerase chain reaction) test (also known as the Amplicor
HIV Monitor Test), Chiron's bDNA (branch DNA test, also known
as Quantiplex) and Organon Teknika's NASBA (nucleic acid sequence based amplification) test. It is important to use the same
laboratory and the same test every time as PCR viral load results
are consistently higher than those obtained with bDNA. For more
information on viral load tests, call the Project inform Hotline
and ask for the Diagnostics Fact Sheet.
Recently, the US Department of Health and Human Services released a set of Guidelines for the Use of Antiretroviral Agents in
the Treatment of HIV-Infected Adults and Adolescents. These
guidelines are summarized in Table 1 on the next page. In short,
they suggest that most HIV-infected people should be treated. The
one general exception is regarding people with the combination

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