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

Case Presentations and Discussions

definitely in order. The combination ofdidanosine and indinavir
requires five fasting (or near-fasting) states a day. Administering
the didanosine once daily may improve adherence to the regimen
and enhance its efficacy. A review of the dietary requirements to
optimize indinavir absorption may also help. At some point in
the future, individualizing the indinavir dose based on blood levels may be indicated, if this is shown to be clinically useful in ongoing studies.
In my opinion, intensifying the regimen by adding another
active drug would carry unacceptable risks of additional toxicity

and the limitations offuture therapeutic options if the more complex regimen were to fail. A lower-risk intervention may be the
addition ofhydroxyurea to enhance the potency of the didanosine, although even this should be done cautiously in light of the
synergistic hematologic toxicity of zidovudine and hydroxyurea.
This case makes the point that all virologic breakthroughs
are not created equal. Management must be individualized,
based on the particular regimen, available options (including
strategies to enhance adherence), and the specific repeated measures of plasma viral load.

i

9/97
10/97
12/97
2/98

9,000,000
11,000
1600
5000

patient, the therapy has failed, evidenced by the viral load levels
at months 3 and 5. Therapeutic failure might result from poor adherence, as adherence is a crucial factor for achieving maximum
reduction of the viral load. However, in this patient, the therapeutic failure is clearly due to infection with a virus that was already
resistant to 2 of the components of the potent drug regimen. This
situation must be increasingly suspected in early-treated seroconverters if the plasma viral load is not below 200 copies/mL by
month 3, or not below 50 copies/mL by month 5 or 6. In this
patient, changing therapy is indicated.
DR JOHNSON: An important question is how common is multidrug-resistant HIV in primary HIV infection?
DR KURITZKES: There is now evidence from the seroprevalence
surveys from Geneva, and from the data accumulating in the
United States, that up to 7% to 10% ofvirus isolates have resistance mutations for the nRTIs, and somewhere between 5% and
7% have mutations associated with resistance to protease inhibitors. This is beginning to support the consideration of more
routine testing of patients with primary infection. If resistance
testing is done, the very first available sample from the patient
should be used. The longer after transmission of the isolate the
testing is done, the greater the chance that a wild-type revertant
might have overgrown, leading to a situation where resistant
virus, lurking as latent provirus DNA in the infected cells, may not
be detected. Clearly, more organized collaborative surveillance
studies among all patients who are identified with primary infection are needed to establish the incidence of primary resistance in
different geographic regions.
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VOLUME 6, OCTOBER 1998

What do you recommend for this patient?
DR BRU N-V ZIN ET: This is a case in which the primary HIV infection was identified very early; the HIV RNA load level was
high and Western blot showed only antibody to HIV p24. The
therapy was initiated early with a potent antiretroviral regimen
containing a protease inhibitor, which is consistent with current
recommendations. In this setting, the viral load can be expected
to decline below 200 copies/mL by month 3 or month 4. In this