Efficacy and Safety of Emtricitabine vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients<SUBTITLE>A Randomized Trial</SUBTITLE>

ContextEmtricitabine is a new, once-daily nucleoside reverse transcriptase inhibitor (NRTI) with potent activity against human immunodeficiency virus (HIV).ObjectiveTo assess the efficacy and safety of emtricitabine as compared with stavudine when used with a background regimen of didanosine and efavirenz.Design, Setting, and PatientsRandomized, 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.InterventionsReceipt 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 MeasurePersistent virological response, defined as achieving and maintaining viral load at or below the limit of assay quantification (≤400 or 50 copies/mL).ResultsAt 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/&#181;L vs 119 cells/&#181;L, 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