Cal Cohen reported on
preliminary 24 and 48 week data for the TIDBID study which compares a Fortovase
twice daily regimen with a Fortovase 3 times per day regimen and a regimen
containing Fortovase (FTV) twice daily combined with nelfinavir twice daily.
This is a randomized,
open-label, phase III study which plans to enroll 825 people. The study primary
endpoint is 24 weeks with a treatment extension to 48 weeks. Patients were
stratified by baseline viral load: 5,000 to 30,000 copies/ml vs >30,000
copies/ml. The patients were also stratified by treatment naïve vs experienced
but I’m only reporting the naïve data here. There were about 3 times as many
naïve enrolled in study than experienced. The range of viral loads in the
<30,000 strata was about 2100 to 30,000 and in the >30,000 strata it was
30,000 to about 3 million.
The study compared:
FTV 1200 mg TID + 2 new
FTV 1600 mg BID + 2 new
FTV 1200 mg BID + NFV
1250 BID + 1 new NRTI (n=135)
As reported by investigators the mean baseline viral loads including all study
participants (naïve & experienced) were about 60,000 copies/ml in the FTV
TID regimen, 52,000 in the FTV BID regimen, and 57,000 in the FTV+NFV arm. The
mean CD4s were about 312 in each arm.
Investigators reported 8%, 11% and 12% failed to return in the FTV TID, FTV BID,
and FTV+NFV BID arms, respectively. Discontinuations for adverse events were 5%,
7%, and 9% in the 3 arms, respectively.
Viral Load Results:
At week 24 in the naïve
group, using an ITT analysis (Intent-To-Treat) for those <400 copies/ml
there were no differences between the 3 arms-- 61% (n=210) had <400
copies/ml in the FTV TID group, 60% (n=213) in the FTV BID group, and 58%
(n=202) in the FTV+NFV BID group.
week 48 On-Treatment analysis by Amplicor and ultrasensitive data showed
about 80% <400 copies/ml (80% in FTV BID, 73% in FTV TID, 75% in NFV+FTV
BID) in all 3 groups and about 60% <50 copies/ml for all 3 arms.
Ultrasensitive <50 copies/ml test, using an ITT analysis at week 24, the
groups had comparable results—44% <50 in the FTV TID arm, 43% <50 in
the TV BID arm and 44% <50 in the FTV+NFV BID arm. There were over 200
individuals in each arm.
Ultrasensitive but with an On-Treatment analysis—60% had <50 in the FTV
TID, 57% in the FTV BID, and 63% in FTV+NFV BID arms.
Cohen said there were
no differences between the three arms when viral loads were above or below
But, it appears that
the baseline <30,000 copy group responds better than the >30,000
group. The baseline median viral load for the <30,000 group is about
13,000 copies/ml, and the baseline median VL for the >30,000 group is
about 129,000 copies/ml. When looking at the 24 week ultrasensitive data
(ITT analysis) for below or above 30,000 copies/ml Cohen said there was a
50% success rate (< 50 copies/ml) in the <30,000 group and 40% had
<50 in the >30,000 group, but there were no differences seen between
the 3 arms.
As well, when looking
at the On-Treatment analysis Cohen said there was a difference in the
responses between the <30,000 and >30,000 group (about 70% vs 50).
These differences may not be so pronounced when using the Amplicor (<400
CD4 increases were
about the same in each arm: +140 at week 24
diarrhea: 15% for FTV
TID, 13% in FTV BID, and 23% in FTV+NFV BID
nausea: 15% in FTV TID,
10% in FTV BID, and 6% in FTV+NFV BID