Transcript XVI IAC Advisory Meeting Toronto 2006

A prospective, randomized, Phase III
trial of NRTI-, PI-, and NNRTI-sparing
regimens for initial treatment of HIV-1
infection – ACTG 5142
Riddler S.A., Haubrich R., DiRienzo G., Peeples L.,
Powderly W.G., Klingman K.L., Garren K.W., George T.,
Rooney J.F., Brizz B., Havlir D., Mellors J.W., AIDS
Clinical Trials Group 5142 Study Team
A5142 Study Design
Multicenter
Randomized
Open-label
Screening
ARV-naïve
HIV RNA >2,000 c/mL
Any CD4 count
LPV/r
LPV/r
SGC533/133
400/100mg
mgBID
BID
EFVXR
600
+ 3TC ++d4T
ormg
TDFQD
or ZDV
LPV/r SGC 533/133 mg BID
+ EFV 600 mg QD
96 weeks
EFV 600 mg QD
+ 3TC + d4T XR or TDF or ZDV
Stratification by:
 HIV RNA > 100,000 copies/mL
 Hepatitis infection
 Selection of d4T, TDF or ZDV
N  250/arm
Primary endpoints*
• Time from randomization to virologic failure (VF)
• VF: 2 consecutive HIV-1 RNA measurements > 200 c/mL after week 32
• Time from randomization to regimen completion
• VF OR treatment-limiting toxicity or intolerance, as assessed by the site investigator to
any regimen component
* Multiple between-arm comparisons and interim analyses  Adjusted significance level = 0.016
Riddler SA, Haubrich R et al., XVI IAC, Toronto 2006, #THLB0204
A5142 Primary Results
• 753 subjects
• NRTI selection (prior to randomization)
– ZDV 42%
– D4T XR 24%
– TDF 34%
• median follow up 112 weeks
• median CD4 182 cells/mm3
• median HIV-1 RNA 100,000 copies/mL
• No differences between arms in baseline
characteristics
Riddler SA, Haubrich R et al., XVI IAC, Toronto 2006, #THLB0204
A5142 Primary Results
Analysis
LPV/EFV
LPV
EFV
P
No virologic failure at 96
weeks
73%
67%
76%
0.006*
Regimen completion at 96
weeks
61%
54%
60%
0.02**
% HIV RNA < 50 at 96 weeks
83%
77%
89%
0.003*
CD4 increase at 96 weeks
268
285
241
0.01***
Grade 3/4 laboratory
45%
33%
32%
---
Grade 3/4 sign/ symptom
20%
19%
18%
---
* LPV vs EFV- other comparisons ns; ** did not meet significance
threshold of 0.016; *** EFV vs both LPV arms
Riddler SA, Haubrich R et al., XVI IAC, Toronto 2006, #THLB0204
Other Key Findings
• No difference in time to treatment
limiting toxicity between groups
• Preliminary analysis of 124 of 227
subjects with virologic failure (additional
samples being analyzed)
– Preliminary resistance analyses show a trend
toward more NNRTI resistance in the LPV/EFV
arm compared with EFV + 2 NRTI.
– Resistance mutations in 2 drug classes
(M184I/V + K103N) were more common in the
EFV + 2 NRTI arm. PI mutations were not found
in the LPV + 2 NRTI arm.
Riddler SA, Haubrich R et al., XVI IAC, Toronto 2006, #THLB0204