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

International AIDS Society-USA

DR HAMMER: The baseline CD4+ cell
count and plasma HIV-1 RNA level are
not described for this case, but one can
infer that there was an excellent response
to the initial regimen of zidovudine/zalcitabine/saquinavir. Assuming that virologic failure has been confirmed by more
than 1 plasma HIV-1 RNA determination
and that possibilities such as nonadherence, intercurrent illness, or vaccination
have been excluded, there are a number
of potential choices for a new antiretroviral regimen. The basic tenet that all
drugs in the regimen should be changed
can be adhered to in this case given
the options available. One option is
to change the nRTI regimen to stavudine/lamivudine and to combine this
with a dual protease inhibitor regimen
such as indinavir/nelfinavir or indinavir/ritonavir, although substantially
more clinical trial data will be needed to
know if these dual protease inhibitor regimens will prove helpful in a circumstance such as this. A second option
would be to combine stavudine/lamivudine with a protease inhibitor such as
indinavir or nelfinavir and an NNRTI
such as efavirenz. It should also be noted

that some patients in whom saquinavir is
failing will respond to the dual protease
inhibitor regimen of ritonavir/saquinavir,
the dual protease inhibitor for which
there is the greatest clinical trial experience. However, as we gain experience
with other dual protease inhibitor regimens, it is perhaps best to try to change
all the drugs if possible. There is no guarantee of success with any regimen, of
course, because of the potential for drug
cross-resistance, toxicities that limit
adherence, etc. Lastly, if the tests are
available, a decision would need to be
made as to whether phenotypic or genotypic resistance testing might assist with
the choice of the alternative regimen.
DR VELLA: The patient started antiretroviral therapy with a regimen that was
clearly effective but whose potency was
not maximal. At this point, with plasma
viral load back to detectable levels, it is
probable that some degree of viral resistance has emerged and a change in the
regimen is desirable. I agree that the
patient might switch to an entirely new
3-drug combination, including a new
protease inhibitor (eg, stavudine/lamivudine/nelfinavir). As an alternative, a regimen including an NNRTI instead of a
protease inhibitor might be considered,
although only scattered data are available
regarding switching from protease
inhibitor-containing regimens to those
including an NNRTI.
8. Why is zidovudine still
included in the different
recommended antiretroviral regimens? Don't we
know from results of the
past io years that there
was no benefit using

DR FISCH L: Zidovudine monotherapy
has been shown to be inferior to combination regimens related to initial
immunologic, virologic, and clinical
responses. Similar data have been noted
with monotherapy with other nRTIs such
as zalcitabine and lamivudine, with
NNRTIs, and with HIV-1 protease
inhibitors, when evaluating immunologic
and virologic responses, and in some settings, clinical responses. Although initial
increases in CD4+ cell counts and
decreases in HIV RNA levels may be
seen, monotherapy regimens result in the
emergence of viral resistance and thus
subsequent loss of benefits. With the use
of monotherapy NNRTI and protease
inhibitor regimens, broader class resistance is likely.
Zidovudine, as with other nRTIs, has
been a cornerstone drug when building
potent triple-drug regimens for the treatment of HIV infection that include either
all nRTIs (eg, zidovudine, lamivudine,
and abacavir), NNRTIs (eg, zidovudine,
lamivudine, and either nevirapine or
efavirenz) and HIV-1 protease inhibitors
(eg, zidovudine, lamivudine, and either
indinavir, nelfinavir, or saquinavir-soft
gel capsules, or dual protease inhibitorcontaining regimens such as ritonavir/
saquinavir).

16

IMPROVING THE MANAGEMENT OF HIV DISEASE