Background: Once daily (QD) dosing facilitates regimen simplification and adherence to antiretroviral therapy. Emtricitabine (FTC) QD is a newly approved nucleoside reverse transcriptase inhibitor compared in this study to twice daily lamivudine (3TC BID).
Methods: Controlled, open label equivalence trial of 440 HIV-1-infected patients with plasma HIV-1 RNA stably suppressed on a regimen of 3TC 150 mg BID, stavudine or zidovudine, and a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Patients were randomized to continue their current regimen or replace 3TC with FTC 200 mg QD. If HIV-1 RNA levels were </= pound 400 copies/ml at 48 weeks in Protocol 303, patients could continue on FTC in Protocol 350. The primary analysis was based on virologic failure and response defined by plasma HIV-1 RNA suppression below 400 copies/ml.
Results: At baseline, the mean CD4 cell count was 525 (FTC) and 533 x 10(6) cells/l (3TC). At week 48 in Protocol 303, the probability of virologic failure was low, 7% (FTC) and 8% (3TC), and the probability of sustained viral suppression at week 48 was equivalent between treatment arms at both the 50 and 400 copies/ml thresholds. The mean increase in CD4+ T-cell percentage was 2.5% (FTC) and 1.7% (3TC). In Protocol 350, the probability of virologic failure was 11% after 4 years on FTC-containing highly active antiretroviral therapy (HAART).
Conclusion: In stably suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine BID. Emtricitabine-containing HAART was associated with a high rate of sustained virologic suppression during 4 years of follow-up.