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Kaletra BID vs LEXIVA BID, Both with EPIVIR and Abacavir QD, in ART-Naμve Patients: The KLEAN Study; Activity/lipids/safety
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Reported by Jules Levin
XVI Intl AIDS Conference, Toronto, Aug 2006
Joe Eron from the ACTG & the University of North Carolina reported the results of this non-inferiority study comparing Kaletra to fosamprenavir at the oral Late Breaker session Thursday Aug 17 in Toronto. A non-inferiority study means that the study was intended to show that one regimen is not inferior to the other regimen, rather than trying to prove that one regimen is superior to the other. Since this study was designed several years ago they did not use the new formulation of Kaletra, the once a day tablets. They used the older twice a day soft-gel capsules. There was a published version of the study results in The Lancet on Aug 5 just before the conference in Toronto, which you can read on the NATAP website.
Background provided by Eron.
Current DHHS guidelines recommend LPV/r (Kaletra) in combination with 3TC or FTC and ZDV as a first-line regimen for ART-naμve subjects.
FPV/r (LEXIVA, TELZIR) has also been shown to be a potent, well-tolerated and convenient regimen in ART-naμve subjects.
ABC/3TC FDC (EPZICOM, KIVEXA) provides for a simplified QD dosing regimen that may enhance adherence.
STUDY DESIGN
Treatment-naμve patients received fosamprenavir (700/100 mg twice daily) + Epzicom [abacavir/3TC FDC (600/300 mg once daily)] or Kaletra (400/100 mg twice daily) + Epzicom [abacavir/3TC FDC (600/300 mg once daily).
Loss of Virologic Response
TLOVR- FDA Algorithm
-- Includes all data for subjects while still on randomized PI
-- Responders are those with confirmed plasma HIV-1 RNA <400 c/mL who are not yet treatment failures
-- A treatment failure is a subject whose plasma HIV-1 RNA never goes below 400 c/mL, or who has confirmed rebound from <400 c/mL, or who discontinues the randomized PI for any reason
Protocol-Defined Virologic Failure
-- Reduction of plasma HIV-1 RNA <400 c/mL with a subsequent increase to ≥400 c/mL on 2 consecutive occasions
-- Failure to achieve plasma HIV-1 RNA <400 c/mL by Week 24
Geographic Distribution
N=878
Analysis Populations
- Intent-to-Treat (ITT) population
--All subjects randomized and enrolled into the study
- Intent-to-Treat Exposed (ITT-E) population
-- Subjects who received ≥1 dose of randomized treatment
- Per-Protocol (PP) population
-- Excluded subjects who had major protocol deviations
- Safety population
--All subjects exposed to any investigational product
Statistical Analyses
Observed (Obs)
--No imputation for missing values
Last Observation Carried Forward (LOCF)
--Missing assessments were replaced by the last non-missing value
Missing or discontinuation equals failure (MD=F)
--All missing assessments, including assessments that occurred after discontinuation of randomized study medication, were considered failures
Time to Loss of Virologic Response (TLOVR)
Conclusions
- FPV/r BID had comparable efficacy to LPV/r BID in this study using an ABC/3TC FDC QD backbone
- Few subjects had protocol-defined virologic failure
- No major PI-associated mutations (IAS-USA) or reduced phenotypic susceptibility emerged to either PI.
- Both regimens were well-tolerated with few study discontinuations due to AEs
- FPV/r and ABC/3TC FDC are now recommended components for initial
antiretroviral therapy in the IAS-USA Adult Treatment Guidelines (JAMA Aug. 16, 2006)
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