Improving the Management of HIV Disease Vol. 6, no. 5 [World Conference on AIDS (12th: 1998: Geneva)]

QUESTIONS TO THE ANTIRETROVIRAL THERAPY AND RESISTANCE TESTING PANELS

therapy. From the didanosine monotherapy arm of ACTG 175 we know that
didanosine "buys" on average at least 2
years of increased CD4+ cell count and
decreased plasma HIV RNA level in early
HIV infection. Data on didanosine and
hydroxyurea suggest that increased plasma HIV RNA suppression occurs with
the combination, even when hydroxyurea
is added after several years of didanosine
exposure. The most efficient use of these
2 drugs may be to add hydroxyurea in
response to evidence of progression (rising HIV RNA level, falling CD4+ cell
count, or development of symptoms).
This must be balanced against the risks
of neutropenia and bone marrow suppression with long-term hydroxyurea use.
DR MONTANER: Current therapeutic
guidelines are based on the principle that
high-level suppression of viral replication
will be associated with decreased morbidity, mortality, and immunologic recovery.
The difference between partially and highly suppressive regimens is largely attributable to the ability of the highly suppressive therapies to minimize the chances of
viral rebound and therefore emergence of
resistance. This is fundamentally responsible for the more profound and durable
benefit associated with highly suppressive
therapies. On the other hand, there is no
doubt that partially suppressive therapeutic strategies have led to improved clinical
outcomes as described by Dr Katzenstein
above.
I would be extremely hesitant to
endorse a policy of using less than highly
suppressive therapy (ie, triple-drug therapy) as this could open the door for policy
makers to embrace suboptimal therapeutic strategies, which in my opinion should
be strongly discouraged.

DR VOLBERDING: Assuming a patient
has established infection (infected for at
least 6 months), it does not matter so
much how long he or she has been infected. As far as we know, the current CD4+
cell count and viral load remain predictors of risk of complication of the disease
and the rate the disease may progress.
This patient has a normal CD4+ cell
count but a rather high viral load. I
would not urge him to begin treatment
but would follow the CD4+ cell count
closely, about every 3 months. I would
recommend treatment if the CD4+ cell
count begins to decline substantially,
particularly if it falls below 500 cells/pL,
and certainly before it reaches 350/pL
or so.

DR YENI: Given the continuum of
increased risk of progression of HIV disease with increasing baseline plasma HIV
RNA level, there is no "magic" threshold
plasma HIV RNA value for deciding
when to initiate therapy in patients with
established HIV infection. The recommended range of 5000 to 10,000
copies/mL is a compromise incorporating some degree of approximation.
In patients tested for plasma HIV
RNA in the absence of recent immunization or ongoing infection, the test variability is 0.3 log (twofold), which is low,
given the spectrum of observed RNA values. Increasing the number of tests to
more than 2, in order to more accurately
assess the baseline plasma HIV RNA
level, would result in an excessive refinement, given the approximation of the
recommended threshold value for therapy. Taking into account other parameters, such as changes in CD4+ cell count
and plasma RNA level over time and
patient commitment to therapy, is more
appropriate at this stage of the decisionmaking process.
DR SAAG: I agree, 2 baseline tests are
generally adequate to make treatment
decisions in this setting. In a patient with
a CD4+ count above 500 cells/pL, most
clinicians will not recommend that antiretroviral therapy be initiated until viral
load values are confirmed to be at least
5000 to 10,000 copies/mL. It would be
unusual for viral load values to fluctuate
between 5000 and 30,000 copies/mL, for
example. Therefore, 2 baseline tests
should confirm whether the viral load is
in the range where treatment should be
initiated; if the levels are in the "observe"
range (below 5000 to 10,000 copies/mL),
follow-up HIV RNA values should be
obtained about every 3 months.

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VOLUME 6, OCTOBER 1998