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Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen

Fischl, Margaret Aa; Collier, Ann Cb; Mukherjee, A Lisac; Feinberg, Judith Ed; Demeter, Lisa Me; Tebas, Pablof; Giuliano, Marinag; Dehlinger, Marjorieh; Garren, Kevini; Brizz, Barbaraj; Bassett, Rolandc; for the Adult AIDS Clinical Trials Group A5116 Study Team

doi: 10.1097/QAD.0b013e328011ddfa
Clinical Science

Objectives: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens.

Methods: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥ 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity.

Results: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively).

Conclusions: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.

From the aDepartment of Medicine, University of Miami School of Medicine, Florida, USA

bDivision of Infectious Diseases, University of Washington School of Medicine, Seattle, Washington, USA

cCenter for Biostatistics in AIDS Research, Harvard School of Public Heath, Boston, Massachusetts, USA

dDivision of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

eDivision of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA

fDivision of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, USA

gIstituto Superiore di Sanitá, Rome, Italy

hDivision of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA

iAbbott Laboratories, Abbott Park, Illinois, USA

jSocial and Scientific Systems, Inc. Silver Spring, Maryland, USA.

Correspondence to M.A. Fischl, University of Miami School of Medicine, AIDS Clinical Research Unit (R-60A), 1800 N.W. 10th Avenue, Miami, Florida, FL 33136, USA. Tel: +1 305 243 3847; fax: +1 305 545 6705; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.