Antiviral Strategies

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stopped at the same time to prevent the development of drug resistance.
Which of the Antiviral Treatments Can Pregnant
Women Use?
Because there are not many well-controlled studies of antiviral
therapies in pregnant women, decisions about treatment regimens
should be made with a physician after weighing the benefits with
the potential risk to the fetus. In addition, pregnant women may
take into account whether or not the drug crosses the placenta
(the part of the sac around the fetus that provides nourishment)
and reaches the bloodstream of the fetus, thereby preventing the
transmission of HIV from mother to child.
Of the nucleoside analogues, only AZT and 3TC have been wellstudied in pregnant women. Both have been shown to be safe and
effective, and both cross the placenta. In animal studies, all nucleoside analogues (except ddl) have caused an increased risk of side
effects in the fetus, but it is not known whether this would be true
in humans. In particular, animal studies of AZT at extremely high
doses showed a higher risk of developing cancer. Because no such
reports have been made in humans with the regular doses of AZT,
the benefits of AZT were deemed to outweigh its risk of causing
cancer in the newborn. Of the NNRTIs, only nevirapine has been
studied in pregnant women and was shown to be well-tolerated,
crossed the placenta and reached effective blood levels in the fetus. Studies of combination therapies with protease inhibitors are
currently in progress. In some animal studies, indinavir and
ritonavir have been shown to cross the placenta. However, some
of the side effects associated with indinavir, liver toxicity and kidney stones, may be more dangerous and more intense in a developing child. Women need to weigh the possible toxicity to the
fetus with the need to prevent HIV transmission in making decisions about treatment during pregnancy.
Which Treatments Can Help Prevent Transmission
of HIV from Mother to Child?
AZT has long been known to be able to reduce the risk of motherto-child transmission of HIV by 70-80% regardless of the mother's
viral load level and is regularly prescribed to pregnant women for
this purpose. The drug is given at the 14th week of pregnancy and
throughout the rest of the pregnancy. It is then given intravenously (in a vein) during labor and is given to the newborn child
for 6 weeks after birth. An ongoing study is evaluating the use of
nevirapine for preventing transmission from mother to child. In
the future, it is likely that more potent combinations will be found
even more effective in preventing transmission than any single
drug alone.

Antiviral Strategies!
DiSCusSion Paper
How Will I Know if Treatment is
Working?
The goal of antiretroviral therapy is to reduce HIV RNA levels
below the limit of detection with the current viral load tests or at
least to fewer then 5,000 HIV RNA copies. When the new, more
sensitive viral load tests become available, the goal will be to fall
below the limit of detection on those tests, which measure down
to 20 copies of virus or less. The indications of a treatment effect
vary somewhat depending on the stage of disease. However, not
everyone is able to bring their viral load levels to below the limit
of detection or to fewer than 5,000 HIV RNA copies. For these
people the minimum change in viral load that indicates the therapies are active is a three fold reduction (0.5 log) in HIV RNA levels. However many physicians believe you need at least ten-fold
reduction (1 log) to have a real impact on disease progression.
People with lower CD4+ cell counts and high HIV RNA measures
may find that viral levels drop more slowly over time, anecdotal
experience suggests that among people in more advanced disease
decreases in HIV RNA happen slower (three to six months).
When is it Time To Change?
The Federal Guidelines recommend that people switch or add new
therapies when their HIV RNA levels return to baseline (or within
1 to 3 fold of pre-therapy levels). "Baseline" means the level of
virus prior to beginning a new therapy regimen. Other researchers believe that this recommendation is not aggressive enough
and recommend people switch or add therapies if their HIV RNA
levels are more than 3 fold higher than their previous results,
signaling the onset of viral resistance. Others fear that changing
therapy too quickly might cause a person to cycle through all the
available drugs too quickly and leave him or her with no further
options. In any case, the decision to switch or add therapies should
be based on two viral load tests spaced about two weeks apart. A
common infection such as the flu, or even a vaccine shot, can
increase HIV RNA levels temporarily. Prior to making dramatic
adjustments in regimens, factor in how other health considerations may be effecting the viral load test results and if necessary,
wait and get another HIV RNA test before making decisions. People
who do not achieve at least a 10 fold (1 log) reduction in viral load
4 weeks after starting therapy may consider changing regimens.
In addition, people whose viral load does not fall below the limit
of detection within 4-6 months of starting therapy should think
about changing, but keep in mind that people with high initial
viral loads may take longer to reach the limit of detection. In addition, it may take longer to reach undetectable for people who
are using the new sensitive viral load tests (20 copies HIV RNA as
the limit of detection).

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