Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV

Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, United States
New England Journal of Medicine (Impact Factor: 55.87). 02/2006; 354(3):251-60. DOI: 10.1056/NEJMoa051871
Source: PubMed


Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere.
We conducted an open-label, noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were randomly assigned to receive either 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 daily plus efavirenz once daily (zidovudine-lamivudine group). The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study.
Through week 48, significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P=0.002). This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen. Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in the tenofovir-emtricitabine group 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 cells per cubic millimeter, respectively; 95 percent confidence interval for the difference, 9 to 55; P=0.002). More patients in the zidovudine-lamivudine group than in the tenofovir-emtricitabine group had adverse events resulting in discontinuation of the study drugs (9 percent vs. 4 percent, respectively; P=0.02). In none of the patients did the K65R mutation develop.
Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs. (ClinicalTrials.gov number, NCT00112047.)

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    • "The PCR products were purified by Gel Purification kit (Bioneer, Global Genomics Partner, Daejeon, Republic of Korea) according to manufacturer's instructions and sequenced in an automated DNA sequencer (ABI PRISM 3730 version 3.0, Applied Biosystems, Foster City, CA). The reverse transcriptase and protease sequences were analyzed by BioEdit software (version 5.0.6), and the Stanford University HIV Drug Resistance Database was used for drug resistance interpretation [Rhee et al., 2003; Campbell et al., 2005; Gallant et al., 2006]. This database categorized resistance as either susceptible or as low, intermediate, or high-level resistance using a mutation penalty score based on published drug resistance and treatment outcome studies as well as in-vitro susceptibility data. "
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    • "Por ejemplo, el estudio de Robbins et al., 2003 (26) reportó una proporción de pacientes con carga viral indetectable del 75%. Similarmente, en el estudio de Gallant et al., 2006 (27), diseñado con el objetivo de comparar un esquema basado en Tenofovir , Emtricitabina y Efavirenz versus el esquema Lamivudina/Zidovudina + Efavirenz, reportó en el brazo de control (Lamivudina/Zidovudina + Efavirenz) una proporción del 73% de los pacientes que lograron indetectabilidad de la carga viral. Por su parte, un estudio abierto con 19 pacientes con el esquema innovador Combivir ® + Stocrim ® realizado en Londres por Portsmouth S et al., 2004 (20), encontró que el tiempo medio para alcanzar una carga viral indetectable fue de 12 semanas (rango 4-36 semanas); tiempo que es similar al que se obtuvo en el presente estudio (12 semanas) (ver figura 2). "
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