- A Randomized, Double-Blind, Multicenter Comparison of Emtricitabine QD to Stavudine BID in Treatment-Naive HIV-Infected Patients (Oral 38)
Authored by F. Raffi, M. Saag, P. Cahn, M. Wolff, D. Pearce, J.M. Molina, J. Hinkle, A. Shaw, E. Mondou, J.B. Quinn, F. Rousseau for the FTC301 Study Team
FTC (emtricitabine, Emtriva) is a potent, once-daily NRTI that has a similar resistance profile to 3TC (lamivudine, Epivir). Dosed as one 200-mg capsule daily, it has been in clinical trials for the past several years, and was recently granted FDA approval in part due to the impressive results of the study presented here. The study was initially presented at last year's ICAAC with 48-week data. This presentation updated those results to 60 weeks.
In this study, antiretroviral therapy-naive patients were randomized to receive either FTC 200 mg daily or d4T (stavudine, Zerit) at standard doses. The remainder of the regimen was ddI (didanosine, Videx) and efavirenz (EFV, Sustiva), both given once daily. Since the study was conducted in a double-blind fashion, all participants had to take pills twice daily. Failure outcomes were defined based on virologic, clinical and tolerability criteria, as outlined in the table below. As noted last year, at week 24 of the study, the Data Safety and Monitoring Board (DSMB) reviewed the trial's data, and found that FTC was significantly better than d4T, recommending that the study be unblinded and that FTC be offered to the d4T-treated patients.
A total of 571 patients were enrolled. As is often the case with studies conducted in multi-national sites, this was a fairly advanced-disease patient population, with the median baseline HIV RNA 4.9 log and the CD4 cell count 318. At the end of 60 weeks, FTC outperformed d4T in all three criteria as follows:
Virologic (never achieving <400 copies/mL or rebound x 2 after <400 copies/mL)
|6 percent||14.5 percent|
Efficacy failure (lost to followup or clinical progression)
|12.5 percent||22.0 percent|
|7.4 percent||16.6 percent|
Looking at the 60-week data, 76 percent of the FTC-treated patients versus 54 percent of the d4T-treated patients achieved the viral load <50 copies/mL threshold, which was statistically significant. d4T therapy was furthermore associated with significantly higher rates of several adverse events -- specifically diarrhea, nausea, abnormal dreams, cough, symptoms of neuropathy, elevated lactate and elevated amylase/lipase.
Although the results of this study clearly favor FTC, it is possible that some of this success is due to the known excess toxicity of the d4T/ddI combination, which has been shown in several studies (most notably ACTG 384) to be a suboptimal NRTI combination. In addition, the study leaves open the question of how FTC/ddI would have compared to 3TC/ddI. (Importantly, in other head-to-head studies FTC has generally been equivalent to 3TC.) Perhaps the most important role for FTC will be the anticipated expanded options for co-formulation -- since FTC has been licensed by Gilead, co-formulation with tenofovir (TDF, Viread) is highly likely.