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Structured Treatment Interruption Based on Genotypic Resistance
Does Not Benefit Heavily Pretreated HIV Patients
The aim of the current study, published
in the current issue of AIDS (October 14, 2005), was to evaluate
the potential benefits of a tailored antiretroviral treatment
interruption with duration based on the observed
reversion of resistance
mutations.
In this open pilot study, 23 patients
with multiple treatment
failure interrupted therapy and underwent genotypic resistance testing.
Salvage
gigatherapy was started when resistance mutations
to at least two antiretroviral drug classes reverted.
The primary endpoint was a fall in
HIV viral
load by > 1 log10 copies/ml after 12 weeks of
salvage therapy.
Results
·
Baseline
median viral load was 5.14 log copies/ml and CD4 cell count 43 x
106 cells/l.
·
Genotypic
resistance testing showed a median of six, two and nine resistance
mutations to nucleoside
analogue reverse transcriptase inhibitors, non-nucleoside
analogue reverse transcriptase inhibitors and protease
inhibitors, respectively.
·
Viral
strains were susceptible to no more than one drug in 17/23 patients.
·
The
median duration of treatment interruption was 24 weeks (range, 12-37),
leading to median changes from baseline of + 0.54 log10 copies/ml
and -30 x 106 cells/l.
·
At
the end of treatment interruption, plasma HIV was susceptible to
at least three drugs in 16/23 patients.
·
After
12 weeks of salvage multi-therapy, only one patient had a decrease
in viral load > 1 log copies/ml.
·
All
baseline resistance mutations recurred after treatment resumption.
·
AIDS-defining
events occurred in two-thirds of patients
during the study period.
The authors conclude, “In HIV-infected
patients with multiple failures and no therapeutic options at baseline,
significant reversion of resistance mutations after prolonged treatment
interruption failed to restore antiviral efficacy of a salvage regimen
and was clinically deleterious.”
09-28-05
Reference
J Ghosn and others. No benefit of
a structured treatment interruption based on genotypic resistance
in heavily pretreated HIV-infected patients. AIDS 19(15): 1643-1647, October
14, 2005.
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