Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV
Joel E. Gallant, M.D., M.P.H., Edwin DeJesus, M.D., José R. Arribas, M.D., Anton L. Pozniak, M.D., Brian Gazzard, M.D., Rafael E. Campo, M.D., Biao Lu, Ph.D., Damian McColl, Ph.D., Steven Chuck, M.D., Jeffrey Enejosa, M.D., John J. Toole, M.D., Ph.D., Andrew K. Cheng, M.D., Ph.D., for the Study 934 Group
Background Durable suppression of replication of the human immunodeficiencyvirus (HIV) depends on the use of potent, well-tolerated antiretroviralregimens to which patients can easily adhere.
Methods We conducted an open-label, noninferiority study involving517 patients with HIV infection who had not previously receivedantiretroviral therapy and who were randomly assigned to receiveeither a regimen of tenofovir disoproxil fumarate (DF), emtricitabine,and efavirenz once daily (tenofovir–emtricitabine group)or a regimen of fixed-dose zidovudine and lamivudine twice dailyplus efavirenz once daily (zidovudine–lamivudine group).The primary end point was the proportion of patients withoutbaseline resistance to efavirenz in whom the HIV RNA level wasless than 400 copies per milliliter at week 48 of the study.
Results Through week 48, significantly more patients in thetenofovir–emtricitabine group reached and maintained theprimary end point of less than 400 copies of HIV RNA per milliliterthan did those in the zidovudine–lamivudine group (84percent vs. 73 percent, respectively; 95 percent confidenceinterval for the difference, 4 to 19 percent; P=0.002). Thisdifference excludes the inferiority of the tenofovir DF, emtricitabine,and efavirenz regimen, indicating a significantly greater responsewith this regimen. Significant differences were also seen inthe proportion of patients with HIV RNA levels of less than50 copies per milliliter (80 percent in the tenofovir–emtricitabinegroup vs. 70 percent in the zidovudine–lamivudine group;95 percent confidence interval for the difference, 2 to 17 percent;P=0.02) and in increases in CD4 cell counts (190 vs. 158 cellsper cubic millimeter, respectively; 95 percent confidence intervalfor the difference, 9 to 55; P=0.002). More patients in thezidovudine–lamivudine group than in the tenofovir–emtricitabinegroup had adverse events resulting in discontinuation of thestudy drugs (9 percent vs. 4 percent, respectively; P=0.02).In none of the patients did the K65R mutation develop.
Conclusions Through week 48, the combination of tenofovir DFand emtricitabine plus efavirenz fulfilled the criteria fornoninferiority to a fixed dose of zidovudine and lamivudineplus efavirenz and proved superior in terms of virologic suppression,CD4 response, and adverse events resulting in discontinuationof the study drugs. (ClinicalTrials.gov number, NCT00112047
[ClinicalTrials.gov]
.)
Source Information
From the Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore (J.E.G.); the Orlando Immunology Center, Orlando, Fla. (E.D.); Hospital de La Paz, Madrid (J.R.A.); Chelsea and Westminster Hospital, London (A.L.P., B.G.); the University of Miami, Miami (R.E.C.); and Gilead Sciences, Foster City, Calif. (B.L., D.M., S.C., J.E., J.J.T., A.K.C.).
Address reprint requests to Dr. Gallant at the Division of Infectious Diseases, Johns Hopkins University School of Medicine, 1830 E. Monument St., Rm. 443, Baltimore, MD 21287, or at jgallant{at}jhmi.edu.
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