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Benefit from Adding the Activity of Several Boosted PIs to Improve
Response to a Salvage Therapy in Advanced HIV Disease
Both
highly potent antiretroviral drug salvage multi-therapy and treatment
interruption (TI) have been suggested to be effective
in HIV-1 infected-patients with multiple treatment failure.
GigHAART-ANRS 097 was the only randomized trial during which an
8-week TI was beneficial in heavily pre-treated patients with multi-drug
resistant virus on resuming a multiple-drug salvage
regimen.
The
aim of this study was to analyze virological and pharmacological
factors associated with a virological
response. Clonal resistance analysis showed that
although the viral population was highly mutated and nearly monoclonal
at baseline, the 8-week interruption therapy allowed the re-emergence
of more susceptible quasispecies to the subsequent salvage therapy,
which were not detected by classical genotypic resistance testing.
The
fact that not every viral clone harbored all resistance viral mutations
could explain a part of the virological response to a six to eight
drug regimen for patients enrolled in the TI group.
This
phenomenon was associated with a transient virological response
after the use of a GigHAART therapy, but was followed by the re-emergence
of baseline resistance pattern and acquisition of additional mutations
in patients failing this strategy.
A
combined factor of protease
inhibitor (PI) concentration and genotypic score,
expressed as a genotypic inhibitory quotient (GIQ), was used to
assess the importance of genotypic resistance and plasma drug levels
in the rate of response to multiple PI combination.
The
authors conclude, “The GIQ of each PI used in the regimen was not
associated with virological success. However, the sum of PI GIQs
was predictive of a virological response.”
“These
results suggest that pharmacological enhancement might overcome
viral resistance and that there is some benefit in adding the activity
of several boosted-PIs to improve the response to a salvage regimen.”
Department of Virology, Pitie-Salpetriere
Hospital-Paris, Paris, France.
10/05/05
Reference
C
Delaugerre and others. Virological and pharmacological factors associated
with virological response to salvage therapy after an 8-week treatment
interruption in a context of very advanced HIV disease (GigHAART
ANRS 097). Journal of Medical Virology 77(3): 345-350. September
19, 2005.
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