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Efficacy and Safety of Emtricitabine vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients
A Randomized Trial
Michael S. Saag, MD;
Pedro Cahn, MD;
François Raffi, MD;
Marcelo Wolff, MD;
Daniel Pearce, DO;
Jean-Michel Molina, MD;
William Powderly, MD;
Audrey L. Shaw, PhD;
Elsa Mondou, MD;
John Hinkle, PhD;
Katyna Borroto-Esoda, MS;
Joseph B. Quinn, MSPH;
David W. Barry, MD;
Franck Rousseau, MD; for the FTC-301A Study Team
JAMA. 2004;292:180-189.
Context Emtricitabine is a new, once-daily nucleoside reverse transcriptase inhibitor (NRTI) with potent activity against human immunodeficiency virus (HIV).
Objective To assess the efficacy and safety of emtricitabine as compared with stavudine when used with a background regimen of didanosine and efavirenz.
Design, Setting, and Patients Randomized, double-blind, double-dummy study conducted at 101 research clinics in North America, Latin America, and Europe. The first patient was enrolled on August 21, 2000; no investigator or patient was unblinded until the last patient randomized completed the week 48 visit on October 24, 2002. Analyses were based on data collected in a double-blind setting with a median follow-up of 60 weeks. Patients were 571 antiretroviral-naive, HIV-1–infected adults aged 18 years or older with viral load levels greater than or equal to 5000 copies/mL.
Interventions Receipt of either 200 mg of emtricitabine once daily (plus stavudine placebo twice daily) (n = 286) or stavudine at standard doses twice daily (plus emtricitabine placebo once daily) (n = 285) plus open-label didanosine and efavirenz, once daily.
Main Outcome Measure Persistent virological response, defined as achieving and maintaining viral load at or below the limit of assay quantification ( 400 or 50 copies/mL).
Results At the interim analysis on June 14, 2002, when the last patient randomized completed 24 weeks of double-blind treatment (median follow-up time of 42 weeks), patients in the emtricitabine group had a higher probability of a persistent virological response 50 copies/mL vs the stavudine group (85% vs 76%, P = .005). This was associated with a higher mean CD4 cell count change from baseline for the emtricitabine group (156 cells/µL vs 119 cells/µL, P = .01 [of note, there was no statistical difference at 48 weeks {P = .15}, although a sensitivity analysis, using an intent-to-treat population with the last CD4 cell count observation carried forward to week 48 showed a difference {P = .02}]). The independent data and safety monitoring board recommended offering open-label emtricitabine based on the interim analysis. The probability of persistent virological response 50 copies/mL through week 60 was 76% for the emtricitabine group vs 54% for the stavudine group (P<.001). The probability of virological failure through week 60 was 4% in the emtricitabine group and 12% in the stavudine group (P<.001). Patients in the stavudine group had a greater probability of an adverse event that led to study drug discontinuation through week 60 than did those in the emtricitabine group (15% vs 7%, P = .005).
Conclusion Once-daily emtricitabine appeared to demonstrate greater virological efficacy, durability of response, and tolerability compared with twice-daily stavudine when used with once-daily didanosine and efavirenz.
Author Affiliations: University of Alabama Research Clinic, Birmingham (Dr Saag); Fundacion HUESPED, Buenos Aires, Argentina (Dr Cahn); CHU de Nantes, Nantes, France (Dr Raffi); San-Borja Arriaran Hospital, Santiago, Chile (Dr Wolff); AltaMed, Los Angeles, Calif (Dr Pearce); Saint-Louis Hospital, Paris, France (Dr Molina); Washington University School of Medicine, St Louis, Mo (Dr Powderly); Gilead Sciences Inc, Durham, NC (Drs Shaw, Mondou, Hinkle, Barry, and Rousseau and Ms Borroto-Esoda and Mr Quinn). Dr Barry is deceased.
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