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

which drugs should be avoided.
DR VOLBERDING: Little is known about
treatment intensification, although clinical trials are now being designed that
should yield data over the next 2 years.
Given this patient's plasma viral load and
CD4+ cell count, intensification could be
considered but probably isn't essential. If
the plasma virus is below detectable levels by the most sensitive assays available,
resistance selection should be minimal
and it is not known whether the CD4+
cells would rise with intensified therapy
if replication is already minimal. If I were
to intensify such therapy, either a protease inhibitor or NNRTI could be used.
In general, I would most readily
move to intensification of therapy in a
patient with a "good" (at least 0.5 log
decrease in plasma viral load) response
to therapy but with more than 500
copies/mL after 8 to 12 weeks of therapy.

Although there are theoretical and anecdotal data to support this approach,
guidelines to help decide whether intensification versus a significant change in
the regimen is the wisest course of action
cannot be provided with our currently
available information.
DR VELLA: Intensification means the
addition of "another" drug to a regimen
that seems quite effective but is unable
per se to induce a maximal HIV suppression (eg, plasma HIV RNA is lowered,
but not to below detectable levels when
measured with a sensitive assay).
Intensification is an early option, if a
potent regimen does not induce a maximal HIV suppression within 24 to 28
weeks, and particularly with patients
starting therapy with very high baseline
plasma HIV RNA levels.
Suboptimal sequential therapy is the
addition of "just" a new drug (instead of
the correct strategy to possibly change all
drug components) to a previously active
regimen that is now failing (eg, a regimen
that induced a good suppression of HIV
replication-to below detection levelbut, after a variable period of time,
begins to fail, as defined by a confirmed
detectable plasma HIV RNA).
27 What do you recommend
fora patientwhobegins
CD4+ cells. and, despite
achieving a plasma viral
load below levels of detection (<so copieslmL) during
the -year treatment periw shows no increase in
CD4+ cell count. Change,
tntensify or continue with

DR SAAG: I would continue with the
same regimen. In the context of viral
replication being the driving force of disease pathogenesis, the current regimen is
achieving near maximal suppression of
replication. You can't do much better
than that. Chances are that the CD4+
percentage has actually gone up, but the
total white blood cell count or total lymphocyte count has decreased, perhaps
due to the regimen itself. In this setting,
it is unlikely that the patient will progress
clinically even with a stable (nonincreasing) CD4+ count. I would "stay the
course.
DR Ku RITZKES: I agree with Dr Saag.
There is no evidence that intensifying the
regimen for a patient with a plasma HIV1 RNA below detection limits will lead to
an improved CD4+ cell response. It is
possible that increases in CD4+ count
may yet occur following a longer period
of maximal virus suppression. If this
patient is taking hydroxyurea, it could
explain the apparent lack of CD4+
response as due to drug-induced
lymphopenia.
28. What is your opinion on
intermittent combination
therapy in developing
countries such as India?
Would such therapy be
cost-effective? Are there
anystudies on this
approach?
DR KATZENSTEIN: Intermittent combinations (of 3 or more drugs) have not
been evaluated as extensively as many of
the nRTIs monotherapies and combinations. In a resource-limited environment
where patients may have difficulties in
accessing a steady supply of drugs and
monitoring, 1 or 2 nRTIs have some

advantages over the use of potent anti
DR RICH MAN: Adding 1 or 2 drugs to
a failing regimen is clearly suboptimal
therapy. Patients in whom failure has
been established have been shown to
have developed resistant virus with
increasing likelihood over time of broadened cross-resistance to the class of drugs
being used. Why then does the concept
of intensification make sense? Recent
data suggest that loss of suppression with
protease inhibitors may be attributable
to outgrowth of wild-type, sensitive virus
and that increase in the potency of
the regimen by the addition of a single
drug to a borderline effective regimen
will resuppress the replicating virus.

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VOLUME 6, OCTOBER 1998