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High
Rate of Virological Failure during Once-daily Therapy with Tenofovir
+ Didanosine 250mg + Efavirenz in Treatment-naive Patients
Once-daily (OD) therapy with tenofovir/didanosine/efavirenz (TDF/ddI/EFV) [Viread/Videx/Sustiva] offers a potentially attractive ART regimen. Co-administration
of TDF and ddI results in higher ddI exposure. The effects of reducing
the ddI dose on intracellular triphosphate levels have not yet been
extensively studied in vivo.
As two recent prospective studies suggested
high rates of virological failure in treatment-naïve pts.
with high VL, the researchers performed an unplanned interim analysis
at week 12.
Of 46 ART-naïve pts. who were enrolled into
this prospective single-arm trial, 39 received medication and completed
week 12. VL and CD4 were measured monthly, plasma trough levels
of TDF, ddI and EFV at week 4 and 12.
Results
·
Mean VL
of 5.04 log10 RNA copies at BL dropped to a mean of 1.96 log10 at
week 12.
·
At this
time 73% and 23% of patients achieved a VL reduction to <400
and <50 c/ml respectively (ITT).
·
VL dropped
to <400 c/ml in a mean of 51 days.
·
Mean CD4
count increased from 288/µl at BL to 410/µl comparable to other
ART regimens.
·
However,
10/39 pts. (25%) demonstrated virological failure at week 12. GT
analysis showed drug resistance mutations to NA (65R, 74I/V) or
NNRTI (101E, 103N, 188C, 190S/E) over time.
·
In two cases primary NNRTI mutations
were detected at BL.
·
6/10 patients
with virological failure had an initial VL >100.000 c/ml and
CD4 <200 cells/µl.
The
authors conclude, “OD TDF/ddI/EFV was safe and led to a strong CD4
cell recovery. However, an unexpected high rate of virological failure
was observed in patients with high BL viral loads and low CD4 counts.
Thus this regimen should not be recommended in these patients.”
University Medical Center Eppendorf, Hamburg,
Germany, Private Practice St. Georg, Hamburg, Germany, Private Practice,
Hannover, Germany, University of Schleswig-Holstein Campus Kiel,
Kiel, Germany, University Medical School, Hannover, Germany, CHU,
Nice, France, 7CHR, Orleans, France,CEA, Gif-sur-Yvette,
France, CHU Bicetre, Paris, France.
08/08/05
Reference
J
van Lunzen and others. High rate of virological failure during once
daily therapy with tenofovir + didanosine 250mg + efavirenz in antiretroviral
naive patients — Results of the 12-week interim analysis of the
TEDDI trial. Abstract TuPp0306 (poster). Program and Abstracts of the 3rd IAS Conference
on HIV Pathogenesis and Treatment. July 24-27, 2005. Rio de Janeiro,
Brazil.
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