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

Case Presentations and Discussions

fold increase in the IC50 to abacavir, the likelihood of response is
extremely low. The likelihood is greater with virus that is sensitive (<4-fold increase in IC50). Although we can expect a response
to an NNRTI, or to abacavir, it may not be sufficient in this pa
tient with advanced-stage disease to produce sustained reduction
of viremia. Possible other drugs to add are the experimental
agent adefovir, or didanosine and hydroxyurea.

Recent genotyping of virus reverse transcriptase showed the following mutations:
V751, F77L, F116Y, Q151M.
What do you recommend for this patient?
DR CLOTET: The genotypic analysis tells us that this patient harbors a multidrug resistant strain of HIV: two mutations observed
in this case confer reduced sensitivity to multiple RT inhibitors.
The multidrug resistant strains have been reported primarily
among patients who were taking zidovudine and didanosine, and
among patients who were taking zidovudine/didanosine and
then zalcitabine. There are anecdotal reports ofmultidrug
resistant strains in patients who have taken stavudine/hydroxyurea/didanosine. It is important to recognize that currently
available genotyping methods (the line-probe assay; LiPA) will
not detect this mutation. However, there are experimental LiPA
assays and selective PCR methods that may be very useful for
evaluating expression of these mutations.
The therapeutic approach that could be recommended
would include 2 protease inhibitors and 1 NNRTI (nevirapine
or perhaps efavirenz). According to the local availability of
drugs in different countries, we might add adefovir or perhaps
hydroxyurea plus didanosine because studies show that hydroxyurea may boost didanosine activity in spite of the presence of the
151 mutation. We have recently reported that the prevalence of
the multidrug-resistant mutation in Spain is 2.7% and has not
changed since 1993. Thus, the prevalence of this mutation in our
country does not support the need for testing for it prior to
changing therapy, except in special cases.
DR LOVE DAY: There are data available for other regions of the
world as well. The ENVA (a European network for quality assurance of molecular virology assays and clinical trials) group defined a 2% prevalence of 151 mutation, and our group from the
Royal Free Hospital in London defined prevalence at 1.6%. It is a
bad mutation, but it does not yet appear to be very prevalent.

VOLUME 6, OCTOBER 1998