|
Salvage Therapy Guided by Rules-based or Phenotype-driven
HIV Genotypic Drug Resistance Interpretation with or without Concentration-controlled
Intervention
It
is not well defined whether concentration-controlled
intervention (CCI) and rules-based human immunodeficiency virus
(HIV) type 1 genotype
drug-resistance interpretation (GI) or virtual
phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy.
In
a prospective, randomized, controlled trial (The
RADAR study), patients were randomized (on a factorial
basis) to change treatment after either GI
or VPI, and they then were further randomized
to the control arm (no CCI) or the CCI arm.
Protease
inhibitor (PI) and non
nucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined
at weeks 1, 4, 12, and 24 of the study.
Results
· Among
230 patients, virological benefit (defined by an
HIV RNA load of <400 copies/mL at week
24) was not statistically different, either
between patients in the GI and VPI arms or
between patients in the CCI and control arms.
· A
virological benefit was found for patients
in the CCI arm, compared with patients in
the control arm, but this benefit was not
statistically significant (56.8% vs. 64.3% at week
4 and 63.6% vs. 74% at week 12).
· Dosage
adaptation was possible for only a fraction of patients, because
of low rates of treatment adherence or patient
refusal to increase dosages.
· In
the logistic regression analysis, independent predictors
of virological
response at week 24 were a PI Ctrough
value and/or an NNRTI Ctrough value
in the higher quartiles (or above cutoff levels)
and a low number of PIs previously received.
Moreover,
receipt of a regimen that contained PIs
boosted with ritonavir was an independent
predictor of virological response.
Conclusions
The
present study did not support the routine use of CCI for patients
undergoing salvage treatment, probably as a result of existing difficulties
associated with its clinical application.
However,
a higher Ctrough value appeared to be correlated with treatment
response. No major differences were found between VPI or GI when
they are used together with expert advice for the selection of salvage
treatment combinations.
06/13/05
Reference
C Torti
and others. A Randomized Controlled Trial to
Evaluate Antiretroviral Salvage
Therapy Guided by Rules-Based
or Phenotype-Driven HIV-1 Genotypic
Drug-Resistance Interpretation With
or Without Concentration-Controlled
Intervention: The Resistance and
Dosage Adapted Regimens (RADAR)
Study. Clinical Infectious Diseases 40(12):
1828-1836. June 15, 2005.
|
