Antiviral Strategies

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of high CD4+ counts (above 500) and low viral load (below 20,000
copies of virus). In this population, the Federal Guidelines recommend "observing" the person and continuing diagnostic testing. However, the Guidelines acknowledge that this is just one
approach and that some will still prefer to offer treatment, even
in this population.
The new Federal Guidelines do not argue that all patients must
be tested. Instead, they describe the recommendations of the researchers, but also point out that patients and physicians must
take many other facts into consideration, such as the person's
readiness to start treatment and concerns about long-term toxicity and drug resistance.

Antiviral Strategies
Discussion Paper
Hit Hard, Hit Early?
A number of researchers are suggesting using a "hit hard, hit early"
strategy for people known to be in or just beyond the acute-infection stage - a period of flu-like illness which often occurs a month
or so after initial infection with HIV. Immediate treatment is already offered to people who have recently been exposed to HIV,
such as health care workers stuck by an infected needle. Increasingly, researchers are interested in testing three-, or four-, drug
combinations (including protease inhibitors) in these people. The
hope of aggressive treatment is to either stop the infection altogether, or at least minimize the potential for long-term damage
by lowering viral load.

Table 1: Recommendations Based on Stage of Disease -
Advanced Stage Disease
All people with AIDS should be treated. When initiating therapy for opportunistic
infections at the same time as initiating antiviral therapy, special care should be
taken to avoid drug interactions. When a patient experiences an opportunistic
infection, he or she should not normally be taken off of antiviral therapy.
Symptomatic, regardless of CD4+ cell counts
All should be treated after consideration of the issues affecting treatment choices.
Asymptomatic with CD4+ counts above 500
There are two unproven approaches to treatment in early, asymptomatic people:
aggressive and conservative. For people with CD4+ cell counts above 500 and a low
viral load, there is no available data to suggest which approach results in longer
survival. Very early, aggressive treatment might lead to longer life. Or conversely, it
might lead to using up the limited supply of therapies too early in the course of
disease by triggering the development of resistance earlier than necessary. In
addition to the general principles and patient preferences, the Guidelines recommend that physicians take into account the relative risk of disease progression
people face based on viral load.
Asymptomatic with CD4+ counts below 500
All should be treated after consideration of the issues affecting treatment choices.
Acute Infection (very early, typically within the first months after
infection)
if infection is suspected, test for HIV viral load. Many, but not all, experts recommend treatment if the test is positive, even at low levels. They believe this offers the
chance of changing the entire later course of HIV disease in the person. However,
people should be made aware of all the potential risks and benefits of such early
treatment. The true long-term effect of immediate treatment is unknown because
current studies are not yet complete. Some experts also recommend treatment for
all people who were infected within the previous six months. Similarly, immediate
treatment is recommended for people with suspected exposure due to accidents in
the healthcare setting.

Lack of data make it unclear if the "hit
hard, hit early" philosophy is always right
for everyone. Some questions around this
strategy include:
Should all HIV-infected people, regardless of CD4+ cell levels or viral
load, be treated immediately with
the most potent multi-drug combinations? Some scientists believe this
is appropriate or at least warrants further study. Others fear even the best
therapies will not work indefinitely
and using them too early in relatively
healthy people, or people with low viral loads might use up our best weapons in many people before they are
truly needed.
In some people, will 2-drug combinations like AZT+3TC be sufficient to
sustain low viral load? In this case,
does adding a protease inhibitor help
in any way? While this approach
might, in a small percentage of cases,
achieve the goal of lowering viral levels below the limit of detection, it still
might not be the best way to extend
the use of currently available options.
For example, using 3TC in this fashion quickly results in the development
of 3TC resistance.
Do people with low viral loads, say
fewer than 5,000 copies of HIV RNA,
require any therapy at all? If viral
load drives disease progression, why
use therapy when viral load is already
low. Does using therapy simply expose

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