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Resistance
Mutations Before and After Tenofovir Regimen Failure
So far, no study has examined the
real impact of tenofovir/
TDF (Viread) regimen failure taking into account
all patients in a current clinical practice. The aim of this study
was to compare the nucleoside
reverse transcriptase inhibitors (NRTIs) mutation
profiles observed before TDF initiation and after TDF-regimen failure.
All patients with genotypic resistance tests
performed in this context were selected from the database of the
department of virology. The patients were categorized in two groups
according to the presence (group I) or absence (group II) of thymidine
analogue mutations (TAMs) documented before starting
TDF.
The proportions of the two groups were compared using Chi-squared
tests. Odds-ratios were analyzed with a regression logistic test.
Results
·
Ninety-six
patients met the criteria.
·
The
median number of TAMs before TDF initiation did not change at failure.
·
The
K65R mutation, absent from all baseline genotypes, developed in
19 of the 96 patients, with an incidence significantly higher in
group II than in group I.
·
In
addition, five genotypes harboring K65R with TAMs or L74V mutation
were observed at failure.
·
The
changes regarding the other NRTI-associated mutations concern mostly
the codons 74, 75, 115, and 118.
·
The
selection of K65R was closely linked to the absence of TAMs at baseline
and to the regimens sparing both protease inhibitors (PIs) and non-NRTIs.
·
The
K65R mutation can emerge even with TAMs or L74V.
·
No
obvious impact was shown on the TAMs or other NRTI mutations, although
a trend towards emergence of some particular mutations was observed.
Department of Virology, Pitie-Salpetriere Hospital, Paris, France.
05/25/05
Reference
M Wirden and others. Resistance mutations before and
after tenofovir regimen failure in HIV-1 infected patients. Journal of Medical Virology 76:297-301, 2005.
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