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

International AIDS Society-USA

retroviral therapy over the short term.
The drugs that offer the most prolonged
activity in partially-suppressive regimens
without the rapid development of highlevel resistance are zidovudine, didanosine (with or without hydroxyurea), and
stavudine. With protease inhibitors,
lamivudine, or the NNRTI drugs (nevirapine, delavirdine, and efavirenz) used

in intermittent courses, the selection of
resistant strains would be expected, with
less effective virus suppression with each
"round" of intermittent therapy.
DR CLOTET: Intermittent combination
therapies could produce the emergence
of drug-resistant virus if maximal HIV
suppression is not achieved. This will

favor the generation of many HIV-1
resistant isolates that could be transmitted, increasing the difficulty in the selection of initial regimens in developing
countries. Intermittent therapies will not
be cost-effective if they do not maximally
suppress HIV-1 replication.

-.RSSANETSI-I
nr on augznging a registarted subpatient with
+ count of So
ovudine
multiple
r added to
line/lamivuent's plasma

DR HAMMER: It is difficult to give a
single response to this question as the
answer truly depends on the options
available to the patient. In the case
described, a good initial antiretroviral
response has been achieved as the CD4+
cell count has risen substantially and the
viral load is detectable but low. Thus, the
patient is at low risk of near-term clinical
progression. In someone who had only
taken zidovudine monotherapy, an
aggressive approach is reasonable,
including 2 new nRTIs such as stavudine/lamivudine, combined with a
potent protease inhibitor. In someone
who has had multiple nRTI exposure, a
dual protease inhibitor regimen combined with an NNRTI such as efavirenz
would be a reasonable option if one

wanted to be aggressive and try to
achieve maximal virus suppression.
Alternatively, a more conservative
approach would be to follow the patient
carefully and defer addition of a protease
inhibitor or NNRTI until there is further
evidence of virologic failure. In someone
in whom a protease inhibitor and nRTIs
have failed, the options become more
limited. The approach in this circumstance depends on the philosophy of the
physician and patient as, for example,
one might choose to wait for a greater
degree of virologic failure before instituting a switch. However, it is advisable not
to wait until the plasma HIV-1 RNA has
risen above the 10,000 to 20,000
copies/mL range as it is becoming
increasingly clear that the ability to successfully suppress virus in an individual
who has experienced failure on a protease inhibitor--containing regimen is
inversely related to the plasma HIV-1
RNA level. If one were to initiate a
change in someone in whom
indinavir/zidovudine/lamivudine has
failed, one option would be to employ a
dual-protease inhibitor regimen with a
change of the nRTIs to stavudine plus
didanosine and to consider addition of
an NNRTI such as efavirenz. It should be
noted that resistance testing may not be
helpful in an individual with a viral load
between 25 and 750 copies/mL as PCR
amplification from the plasma is variable

at these low levels, although the technology is continuously improving.
DR FISCH L: For patients with advanced
HIV disease who had taken nRTIs,
adding lamivudine and indinavir provided clinical and survival benefits but did
not necessarily result in maximal suppression of HIV replication as measured
by both HIV RNA plasma levels and viral
culture. Therefore, for the patient with
prior zidovudine experience, a new regimen should include 2 new nRTIs, excluding zidovudine, and a protease inhibitor.
Alternative regimens with 2 protease
inhibitors, such as ritonavir/saquinavir,
or an NNRTI, such as efavirenz, rather
than a single protease inhibitor may be
considered.
A similar philosophy should be used
for multiple nRTI experience: a combination of 3 new drugs, ones the patient has
never taken and based on treatment history to which the virus is still likely to be
susceptible. Phenotyping of the virus
may assist the physician in identifying
which drugs not to use. Such combination regimens can include nRTIs,
NNRTIs, and 1 or 2 protease inhibitors.
Regimens for protease inhibitor failures are more difficult to determine but
should include 3 to 4 new drugs, whenever possible, to which the virus is still likely to be susceptible. Again, phenotyping
of the virus may assist the physician in

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IMPROVING THE MANAGEMENT OF HIV DISEASE