|
|
Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV.
Gallant JE, DeJesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, Lu B, McColl D, Chuck S, Enejosa J, Toole JJ, Cheng AK, Study 934 Group.
N Engl J Med
2006 Jan 19;354(3):251-60.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.)
Go to
PubMed entry
|
Reviewed by
Susa Coffey, MD
Comment
This large randomized controlled trial compared 2 treatment regimens designated by the U.S. Department of Health and Human Services as the "Preferred" nonnucleoside reverse transcriptase inhibitor-based regimens for antiretroviral-naive individuals. Two groups of patients, well-matched for baseline characteristics, were given efavirenz combined with either emtricitabine + tenofovir or lamivudine + zidovudine.
At 48 weeks of follow-up, the emtricitabine + tenofovir + efavirenz group had significantly higher rates of HIV RNA suppression to <500 copies/mL (84% vs 73%, p = .002) and to <50 copies/mL (80% vs 70%, p = .02) compared with the lamivudine + zidovudine + efavirenz group, and had greater gains in CD4 cell counts.
Significantly more patients in the lamivudine + zidovudine group discontinued the assigned treatment because of adverse events, with anemia as the most common treatment-limiting problem in this group. No significant differences in renal function were seen between treatment groups. In patients with virologic failure, genotypic analysis revealed a preponderance of efavirenz resistance mutations, with or without M184V/I. Importantly, no patients developed the K65R mutation. Thus, the initial regimen emtricitabine + tenofovir + efavirenz appeared to be more effective and better tolerated than lamivudine + zidovudine + efavirenz.
The emtricitabine + tenofovir + efavirenz regimen comprises only 2 tablets, taken once daily. A single-pill combination of all 3 drugs, emtricitabine + tenofovir + efavirenz, may be manufactured soon, and may further improve adherence to and acceptability of antiretroviral therapy in certain populations in the United States and elsewhere.
|
