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

International AIDS Society-USA

A change to a regimen with at least 2 new
drugs will be made. The patient's virus
was sent for phenotypic analysis (5/98) to
evaluate possible drug options. The results
for analysis of the reverse transcriptase inhibitors are as follows:

This case gives rise to several questions:
What is the role of phenotyping in salvage
decisions? What is the likelihood that these
isolates will respond to the nonnucleoside
reverse transcriptase inhibitor (NNRTI) and
protease inhibitors? What is the role of
viral genotypic and phenotypic testing in
predicting subsequent viral load response?
DR MELLORS: This is a good example where susceptibility
testing might help to identify the cause of treatment failure. This
patient has a high plasma viral load and a CD4+ cell count of 180
cells/pL, and is taking antiretroviral therapy. Resistance to the
approved and experimental protease inhibitors has been identified, making poor adherence an unlikely cause of the persistent
plasma viremia. One option is to wait for several new drugs to become available and change the entire regimen. But I do not think
this patient can wait, so I would try to put together a regimen
from available options.
Although the virus appears to be susceptible to zidovudine,
the prolonged history of prior zidovudine use argues against its
use now as recycling might allow emergence of a resistant mutant
very quickly. The treatment history and susceptibility testing
suggest that the current options include didanosine, stavudine,
zalcitabine, perhaps the experimental drug abacavir, and an
NNRTI. However, this patient has taken didanosine and stavudine in the past and it is not known if resistance to these compounds has developed and is now latent. Viral resistance to
stavudine may not necessarily be associated with phenotypic resistance. We would expect that this patient will respond to an
NNRTI (perhaps efavirenz), but unless that is partnered with additional potent agents, we would expect resistant mutants to
emerge rapidly. Unfortunately, potential partners are few. Abacavir could be an option. There are data with nRTIs and protease
inhibitors that show that the baseline phenotype is predictive of
response, particularly with abacavir. If there is a greater than 8 -
Drug
Zidovudine
Lamivudine
Didanosine
Stavudine
Zalcitabine
Nevirapine
Delavirdine
Abacavir*
Efavirenz

IC50 results
<4-fold S
>10-fold R
<4-fold S
<4-fold S
<4-fold S
<4-fold S
<4-fold S
<4-fold S
<4-fold S

* experimental drugs at this time; R indicates resistant, S indicates susceptible
IMPROVING THE MANAGEMENT OF HIV DISEASE