A prospective, randomized, Phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection

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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

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A5142 Study Design
LPV/r 533/133 mg BID EFV 600 mg QD
LPV/r SGC 400/100 mg BID 3TC d4T XR or TDF
or ZDV
Multicenter Randomized Open-label
LPV/r SGC 533/133 mg BID EFV 600 mg QD
96 weeks
Screening
ARV-naïve HIV RNA gt2,000 c/mL Any CD4 count
EFV 600 mg QD 3TC d4T XR or TDF or ZDV

• Stratification by
• HIV RNA gt 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 gt 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
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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
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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 lt 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
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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