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

International AIDS Society-USA

tain whether the patient has been adherent to the regimen, whether there are
pharmacologic or gastroenterologic reasons for suboptimal plasma levels of
drug, and whether the detectable levels
are confirmed on repeat testing. Because
options are limited, changes should not
be made without compelling reasons. On
the other hand, newer data suggest that
delayed change may diminish future
options. Therefore, concern about impending failure dictates closer monitoring..8. This patient is currently
taking 2 nRTIs and indinavir. He has extensive
previous exposure to all
antiretrovirals except the
NNRTIs. Plasma viral load
is 125 copies/mL for the
past 2 years on stable
therapy. Would you add
an NNRTI (eg, efavirenz),
add another protease
inhibitor, change all drugs
in the regimen, or not
make any changes?
DR MONTAN ER: The case described
poses an extremely difficult but real clinical situation. There is an increasing number of patients who arrive at the clinic on
triple-drug therapy regimens consisting
of 2 nucleosides plus a potent protease
inhibitor with a low plasma viral load
and a history of prior plasma viral load
rebound while on all other available
agents. In these patients, despite the
absence of controlled clinical trial data,
we feel that intensification of the treatment is warranted in order to avoid continued evolution of the virus and ultimately high-level resistance to all available drugs. One possible approach would
be to stop the current regimen and then

to use hydroxyurea plus didanosine and
possibly stavudine and/or lamivudine
plus ritonavir and saquinavir in addition
to an NNRTI.
i. In the setting of protease
inhibitor failure, should a
protease inhibitor still be
maintained in the regimen
in order to hit that target?
DR SAAG: It depends. The likelihood of
success of a protease inhibitor working
after failure of a previous protease
inhibitor is dependent upon the situation
and the mechanism of failure. If the first
protease inhibitor induced only a few
mutations that do not confer cross-resistance to the subsequent protease
inhibitor, there is a reasonable chance of
success for the new protease inhibitorcontaining regimen. Conversely, if multiple mutations that confer cross-resistance exist, the chance of success is much
lower. In this setting, dual protease
inhibitor therapy, along with 2 other
drugs that the patient (ideally) has not
taken previously, may be necessary.
However, success with this approach is
variable. Many clinicians adopt a strategy
of changing therapy relatively early when
their patients experience a confirmed
rebound of viral load (eg, 500 to 5000
copies/mL, confirmed) in order to minimize the emergence of multiple mutations
that will confer cross-resistance.
2Where do you recommend
the use of zalcitabine? For
retreatment? When phenotypic testing shows that
th HIV RNA strain is sen
DR FISCHL: Zalcitabine has been shown
to have modest antiretroviral activity
when combined with other nRTIs in
patients who are antiretroviral treatment-naive. However, several studies
have shown that zalcitabine-containing
regimens are less potent than other nRTI
combinations in patients with prior antiretroviral treatment experience. This has
led to limited use of zalcitabine when
constructing alternative regimens for
patients with prior nRTI experience,
regardless of resistance studies.
21. A patient started zidovudine/lamivudine/indinavir when his CD4+
count was 350 cells/pL
and plasma viral load
was 4oo00,000ooo copieslmL.
At year his CD4+ count
is 700 cells/pL, and plasma viral load is below
400 copies/mL, but he
becomes concerned
about protease inhibitor
side effects. Would you
recommend changing the
protease inhibitor in the
regimen to an NNRTI? If
so would you recommend switching one or
both of the nRTIs in the
regimen?
DR YEN I: The short- and long-term consequences of switching the protease
inhibitor for an NNRTI in patients with
viral load levels below detectable limits
on 2 nRTIs plus a protease inhibitor is
currently under investigation. Until more
information is available, such a strategy
cannot be uniformly recommended. If
the patient is concerned about, but not
experiencing, protease inhibitor side

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