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Virological
and Pharmacological Parameters Used to Predict the Response to Lopinavir-Ritonavir
in Heavily PI-experienced Patients
The genotypic inhibitory quotient
(GIQ) has been proposed as a way to integrate drug exposure and
genotypic resistance to protease
inhibitors
(PIs) and can be useful to enhance the predictivity of virologic
response for boosted
protease inhibitors.
The
aim of this study was to evaluate the predictivity of the GIQ in
116 protease inhibitor-experienced patients treated with lopinavir-ritonavir
(Kaletra).
The
overall decrease HIV-1 RNA from baseline to month 6 was a median
of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1
RNA below 400 copies/ml at month 6. The overall median lopinavir
study-state C(min) concentration was 5,856 ng/ml.
Using
univariate linear regression analyses, both lopinavir GIQ and the
number of baseline lopinavir mutations were highly associated with
virologic
response through 6 months.
In
the multivariate analysis, only lopinavir GIQ, baseline HIV RNA,
and the number of prior protease inhibitors were significantly associated
with response.
When
the analysis was limited to patients with more highly mutant viruses
(three or more lopinavir mutations), only lopinavir GIQ remained
significantly associated with virologic response.
Conclusions
Based
on these results, the authors conclude, “This study suggests that
GIQ could be a better predictor of the virologic response than virological
(genotype)
or pharmacological (minimal plasma concentration) approaches used
separately, especially among patients with at least three protease
inhibitor resistance
mutations.”
“Therapeutic
drug monitoring (TDM) for patients treated by lopinavir-ritonavir
would likely be most useful in patients with substantially resistant
viruses.”
Department of Virology, Pitie-Salpetriere
Hospital, 83 Boulevard de l'hopital, 75013 Paris, France.
05/11/05
Reference
A
G Marcelin and others. Virological and pharmacological parameters
predicting the response to lopinavir-ritonavir in heavily protease
inhibitor-experienced patients. Antimicrobial
Agents and Chemotherapy 49(5): 1720-1726. May 2005.
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