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

Case Presentations and Discussions

sient 1-log drop in HIV RNA over the next
3 months. Nine months after the switch,
the HIV RNA level is 60,000 copies/mL
and the CD4+ count continues to remains
stable at 300 cells/pL.
The patient's adherence is good. What is
going on?
DR MONTAN ER: Obviously this is a difficult case that brings up
the question of discordant responses. However, looking back at
the history of antiretroviral therapy, particularly with dual nucleosides, this has always been an issue. For example, in the ACTG
175 and DELTA studies, early rebound in viral load was associated with a delayed CD4+ count decrease. The lag time was even
longer if clinical events are considered. I suspect, although it has
not yet been demonstrated, that what we are seeing with triple
therapy regimens is a magnification of this effect. My prediction
is that in due course, these patients will have declines in the
CD4+ counts. In the meantime, that does not mean that they
have not been protected. Of course they have been.
DR VE LLA: What would the panel recommend for this patient?
Some options might include:
1. No change
2. Intensify current therapy: eg, add hydroxyurea
and/or NNRTI
3. Change to new drugs/classes
- without nRTI recycling: eg, didanosine/hydroxyurea/
NNRTI/protease inhibitor
- with nRTI recycling: eg, zidovudine/lamivudine plus
didanosine/hydroxyurea/NNRTI/protease inhibitor
4. Interrupt therapy

DR KATZENSTEIN: There is no question that protease inhibitors
are gone as an option. Resistance testing of the reverse transcriptase of this patient might be considered, because all of our clinical experience tells us that we are no longer benefiting the patient
with the protease inhibitors. His viral load is increased and given
that he has taken 3 protease inhibitors over the past 11/2 years to
2 years, we are unlikely to have any effective protease inhibitor. I
would suggest we change to multiple drugs including hydroxyurea and didanosine, as well as perhaps adefovir. Hopefully
soon we will have other nRTIs available so I would change all
classes of drugs, but I don't see a reason to change to a new protease inhibitor; it should be discontinued.
I agree that the discordancy that we are seeing is one that
we can feel some ease with respect to the patient's immediate risk
of progression, but I do have concern about his long-term prognosis raised by the rising plasma virus load.
DR VELLA: How might the recommendations change in this
case, if the CD4+ cell count were low (ie, about 80 cells/pL)?
DR Ku RITZKES: The difference here with this patient is that the
CD4+ count has dropped to 80 cells/pL along with the rise in
HIV RNA. Something different clearly needs to be done, but exactly what to do is a much more difficult question. I am again
tempted to move to the addition ofhydroxyurea with an NNRTI
with perhaps also adefovir if it were available, because in this patient, protease inhibitors are most likely exhausted as an option.
If clinical trials were within reach, then the possibility of enrollment in a study of one of the "second generation" protease inhibitors could be considered or some of the other studies in antiretroviral experienced patients that are planned or under way.
I would be concerned about the use of zidovudine in a regimen
that includes hydroxyurea because of likely synergistic bone marrow toxicity. There are really no data about adding a second
NNRTI so my recommendation would be to try didanosine/
hydroxyurea/an NNRTI and adefovir, if it were available.
DR SAAG: I would add an important note regarding the use of
adefovir. Some data were presented at this meeting demonstrating a significant increase in the antiretroviral activity ofadefovir
against clinical isolates containing an M184V mutation. Specifically, the use of adefovir in patients harboring virus without the
M184V mutation results in about a 0.4- to 0.6-log reduction in
viral load. When used in patients who have M184V mutant

viruses, the level of activity was on the order of 0.8- to 1.0-log
VOLUME 6, OCTOBER 1998

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