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

International AIDS Society-USA

pathogenesis. Prospective controlled trials, such as ACTG 384, are attempting to
clarify the true incidence and whether
this problem is related to treatment with
protease inhibitors or is related to potent
virus suppression by any regimen. It is
not clear whether "protease-sparing" regimens will prevent this complication. The
risks of therapy and the risks of delay
should be discussed with the patient, and
an informed decision should be made. In
my view, the risks of not treating probably outweigh the risks of significant
lipodystrophy.

ise of
lidanoa
'o mg q
mg q
able"
n rove

the didanosine dose, or move the didanosine dose to a midday dose if needed. Of
note, current data (October 1998) indicate that bid dosing of indinavir is significantly less effective than tid dosing as a
component of potent antiretroviral
therapy.
13. In a therapy-naive, HIVseropositive patient with
CD4+ count of 20 cells/t,
will starting a very aggressive 4-drug or 3-drug therapy cause the subject to
have a larger CD4+ pool?
Will this thus raise the
plasma HIV RNA level?
DR HAMMER: There is the theoretical
possibility that the greater CD4+ cell
count rise induced by the most potent
antiretroviral drug combinations available will increase the target cell population and thus paradoxically raise the
plasma HIV-1 RNA level. Such a possibility has been raised as one of the factors
involved in the failure of simplified maintenance regimens in the ACTG 343
induction maintenance trial. In that
study following successful induction on a
regimen of indinavir/zidovudine/lamivudine, one of the predictors of failure in
patients randomized to less intense regimens following virologic suppression was
an early rise in the CD4+ cell count during induction. This, however, is a much
different circumstance than the one
described in this case. An individual with
a CD4+ cell count of only 20/pL and presumably a substantial plasma HIV-1 RNA
level is at high risk of disease progression
and is deserving of the most potent treatment. Successfully suppressing virus
replication to the greatest degree possible
(ie, to <20-50 copies of HIV RNA/mL)
will clearly limit the risk that new CD4+

cells will become infected. In fact, the
greatest way to protect proliferating
CD4+ cell counts is to maximize viral
suppression. Further, it should be noted
that successful antiretroviral therapy is
associated with a diminution in activation markers on the surface of CD4+
cells, thus making them theoretically less
able to support virus replication. Finally,
ACTG 320 demonstrated that clinical
disease progression can be significantly
slowed by the use of more potent (ie, a
3-drug regimen including a protease
inhibitor) compared with a less potent
regimen (ie, a dual nRTI combination).
Thus, all the evidence weigh in favor of
being aggressive in this case.
I 4.Is there a preferred antiretroviral regimen for an
HIV-seropositive patient
with Kaposi's sarcoma?
DR VOLBERDING: Most patients with
Kaposi's sarcoma should be treated with
aggressive protease inhibitor-containing
drug combinations. Clearly, these
patients have a complication of HIV disease and require aggressive antiretroviral
therapy. A response of the Kaposi's sarcoma may occur with protease inhibitorsparing regimens, but much more experience has been gained with the protease
inhibitor-containing regimens as elements of the regimen, so I would probably recommend including them until
more experience is gained with other
approaches. There are no specific combinations of antiretroviral drugs that have
demonstrated efficacy for Kaposi's sarcoma, but if aggressive chemotherapy is
required, attention must be paid to the
possibilities of drug interactions and
toxic effects, especially neutropenia and
peripheral neuropathies.

DR KATZENSTEIN: Most adherence
studies indicate that the "midday" dose is
the most frequently missed one. Patients
often have difficulty, with work and travel schedules, remembering to take the
midday doses. Patients are always looking for the most convenient bid dosing
schedules. A potential difficulty of the
regimen proposed could be the ability to
consistently take 400 mg of didanosine
(on an empty stomach) followed 30 to 60
minutes later by indinavir (indinavir
should be taken on an empty stomach or
with a light meal or snack, if needed for
better tolerance). There may be only a
small advantage to once-daily dosing
didanosine while all other drugs in the
combination are taken twice or three
times daily. I would begin this regimen
with careful monitoring of the patient's
tolerance for a large, early-morning dose
of didanosine, with plans to either split

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