Antiviral Strategies

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nation doesn't quite succeed in stopping measurable viral
activity, many researchers believe it may be wise to either
change two of the drugs, or perhaps add a fourth drug. It
makes sense to try and fully suppress viral replication if this
can be done with a reasonable quality of life. When this goal
cannot be achieved, people should realize they can still benefit from therapy and that longer-term solutions may become
apparent when additional therapies are available.
Using a drug exactly as prescribed is critical to success.
Using an inadequate dose, reducing the dose below the prescribed level, or failing to take the drug at regularly spaced
intervals will increase the risk of developing viral resistance.
If intolerance or side effects develop, it is often better to try
to overcome the side effects than to immediately change the
regimen. If side effects aren't manageable, it is better to temporarily stop the drug rather than reduce its dose. This runs
counter to common clinical practice with the nucleoside analogue reverse transcriptase inhibitors or NARTIs (e.g. AZT,
ddl, ddC, d4T and 3TC), in which physicians routinely lowered doses as a way of dealing with side effects. The fastest
way to develop resistance to antiviral drugs is to use them at
an inadequate or inconsistent dose level.
If you need to take a "drug holiday," it is best to stop all
antiviral therapies at the same time rather than just stopping one drug. There are a number of reasons that people
may need to stop taking their medications, including side
effects, drug interactions, pregnancy or their drug supply runs
out. There are no studies that indicate how many days, weeks
or months "vacation" from antiviral drugs is likely to increase
drug resistance. However, it is clear that if a person needs to
stop therapy for whatever reason, it is best to stop taking all
drugs at the same time. In the presence of a partially effective
antiviral regimen, the virus is able to reproduce, mutate and
develop resistance to the remaining therapies. However, if all
drugs are stopped simultaneously, there is no selective pressure for the virus to mutate.
What Therapy Should I use?
Ideally, the best drug combination to use would be the one that is
most successful in reducing viral load below the limit of detection for the longest time, while preserving quality of life. In the
real world, what is best for the individual is sometimes different
from what works best in a clinical trial. Some drugs and combinations are clearly more potent than others. In some instances, the
differences between various combinations are not clearly defined,
largely because comparative studies have not been done. Drug
manufacturers try to avoid conducting studies that make direct
comparisons. While this may be good for them, it often leaves the
patient in the dark. Still, a reasonable amount of data are avail
Antiviral Strategies
Discussion Paper
-TABLE: Federal Recommendations on
Combination Therapy
Choose one drug from Column A (highly active protease inhibitors) and one combination from Column B (NARTIs)

COLUMN A
Indinavir
Ritonavir
Nelfinavir

COLUMN B
AZT + ddi
d4t+ ddl
AZT + ddC

AZT + 3TC
d4T + 3TC
Alternative Combinations
The following combinations are recommended as alternative
combination regimens.
Nevirapine + 2 NARTIs (one combination from column B above)
Saquinavir+ 2 NARTIs (one combination from column B above)
Not generally recommended: 2 NARTIs (column B above)
The following combinations are not recommended:
d4T + AZT
ddC + ddi
ddC + d4T
ddC + 3TC
able which allows us to conclude that some drugs are "highly active" antivirals and some are less active. In general, the most effective combination therapy regimens contain at least two "highly
active" antivirals, usually added to a third drug of similar or lesser
potency but which works in a different way. Within the realm of
combinations with adequate overall potency, other factors become
important in selecting a therapy regimen.
Quality of Life Issues
Tolerance can be as important as the potency of a drug. If you
can't take a drug consistently as prescribed, its potency is irrelevant. Lack of adherence to the protocol will quickly contribute
to the development of drug-resistant mutations of HIV. When
choosing a combination, consider the daily pills count
(antiretrovirals, drugs for opportunistic infections and everything
else), when they will be taken, whether they can be taken with
other medications and whether they can be taken with food.
It is easiest to combine drugs that require similar conditions for
their use (with food, without food etc.). Otherwise, one's life becomes dominated by drug schedules. Also it is best to avoid mix
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