1. 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

2. Multicenter Randomized EFV 600 mg QD + 3TC + d4T XR or TDF or ZDV
A5142 Study Design
LPV/r SGC 400/100 mg BID
+ 3TC + d4T XR or TDF or ZDV
LPV/r 533/133 mg BID
+ EFV 600 mg QD
Multicenter Randomized
Open-label
LPV/r SGC 533/133 mg BID
+ EFV 600 mg QD
Screening
96 weeks
ARV-naïve
HIV RNA >2,000 c/mL
Any CD4 count
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

3. 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
** the comparison of time to regimen completion did not meet the significance threshold of p < 0.016
Riddler SA, Haubrich R et al., XVI IAC, Toronto 2006, #THLB0204

4. 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%
** the comparison of time to regimen completion did not meet the significance threshold of p < 0.016
* 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

5. No difference in time to treatment limiting toxicity between groups
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