Simplification Therapy with Once-daily Didanosine, Tenofovir and Efavirenz: The
EFADITE Trial
High
pill burden and unwanted adverse side effects have affected the success of HAART.
As a result, clinicians and patients are looking for potent, safe and convenient
regimens.
In
this open, prospective, multicentre, comparative study HIV patients on HAART and
with plasma HIV-1 RNA <50 copies/ml for longer than 6 months were switched
to tenofovir (Viread),
didanosine
(Videx) and efavirenz
(Sustiva) (QD arm) or remained on the same treatment regimen (control
arm).
Patients
with grade 4 toxicities or plasma HIV-1 RNA values repeatedly >1000 copies/ml
discontinued the study.
Results
390 patients were included in the trial (309 in
the QD arm and 81 in the control arm).
The main
baseline characteristics were well balanced between groups.
In the QD arm, 41% of patients received
high (standard) didanosine doses and 59% received reduced doses.
At 12 months,
plasma HIV-1 RNA <400 copies/ml was attained in 66% of QD patients and 73%
of controls in the intent-to-treat (ITT) analysis (P=NS).
However, the number of individuals
with HIV-1 RNA <400 copies/ml in the QD arm was 56% versus 71% when comparing
the use of high versus low didanosine doses (P=0.007).
Treatment
discontinuation occurred in 87 QD cases (28%) and 17 controls (21%).
Twenty QD
individuals (6.5%) and 2 controls (2.5%) discontinued because of virological failure
(P=NS).
The median CD4+ cell count change
at 12 months was –26 and +27 cells/µl in QD patients and controls, respectively
(P=0.001).
In individuals
who attained HIV-1 RNA <400 copies/ml, CD4+ cell changes were –25 and +15 cells/µl
in QD patients and controls, respectively (P=0.001).
CD4+ cell
declines in the QD arm were significantly greater in patients taking high versus
low didanosine doses (–59 versus –15 cells/µl; P=0.04).
The lipid
profile improved significantly in the QD arm, particularly in patients who were
on protease inhibitors prior to simplification.
Based
on these results, the study authors conclude, “Simplification to didanosine–tenofovir–efavirenz
provides a virological suppression rate at 12 months similar to that seen in patients
who do not change therapy, as long as low didanosine doses are administered.”
“Decreases
in CD4+ cell levels in patients in the QD arm (especially decreases seen with
high didanosine doses) and dyslipidemias along with less convenient pill burden
and schedules in controls were the main long-term concerns for each option.”
12/02/05
Reference
A
Barrios and others (for the EFADITE Study Group). Simplification
therapy with once-daily didanosine, tenofovir and efavirenz in HIV-1-infected
adults with viral suppression receiving a more complex antiretroviral regimen:
final results of the EFADITE trial. Antiviral Therapy 10(7): 825-832. 2005.
