In 2001, the U.S. Food and Drug Administration granted the approval of emtricitabine (FTC, Emtriva) for the treatment of HIV infection in combination with other antiretroviral agents. It is a synthetic nucleoside analogue of cytidine very similar to the already well-known lamivudine (3TC, Epivir).

Structurally speaking, these two nucleosides, emtricitabine and lamivudine, are very similar, with the exception of an added fluorine in the emtricitabine molecule. That small structural difference enables emtricitabine to maintain potent antiviral activity and results in a longer intracellular half-life.

Few large, randomized studies have been conducted with emtricitabine in naive and experienced populations. Due to their similarities, most of the clinical and safety data attributed to emtricitabine has been extrapolated from previous studies using lamivudine.

Several presentations at this conference compared emtricitabine to lamivudine in different patient populations. One of these presentations provides the preliminary results of the Gilead Study 934, which directly compared zidovudine/lamivudine (AZT/3TC, Combivir) to tenofovir (TDF, Viread)/emtricitabine in antiretroviral-naive patients. Those results will be discussed at a late-breaker presentation tomorrow.

Two other studies presented at this meeting shed more information regarding the efficacy, safety and tolerability of emtricitabine in different patient populations.

The first study (H-559) is a comparison between regimens containing emtricitabine plus zidovudine (AZT, Retrovir) and regimens containing lamivudine plus zidovudine. In this rollover study, presented by Dr. Benson and colleagues, patients previously enrolled in the Gilead Study 303 who had virologic suppression at week 48 were allowed to participate.

Patients already taking emtricitabine plus zidovudine plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) were continued on the same therapy. Patients on lamivudine plus zidovudine plus an NNRTI or a PI were switched to emtricitabine plus zidovudine plus their current NNRTI or PI.

Virologic and immunologic responses, as well as long-term safety, were monitored for over 3 additional years. The mean follow-up of these patients on their new therapy was 143 weeks. No significant differences regarding the efficacy and safety among HIV-1-infected adults on a stable HAART regimen who switched from lamivudine to emtricitabine were found in this study.

Evaluating Emtricitabine Safety in HIV/HBV Patients

The second study (H-560) was geared more toward the evaluation of emtricitabine safety and tolerability in patients infected with HIV and/or hepatitis B (HBV). For this analysis, the investigators grouped the safety data from 3 different studies that compared emtricitabine to either lamivudine or stavudine (d4T, Zerit): Gilead 301, 302 and 303. They then compared these results to the safety data observed in the emtricitabine B-301 study. This last study was conducted in HBV-monoinfected patients who received either emtricitabine or placebo.

The overall safety results in those 3 studies using emtricitabine in HIV-infected patients were similar to the results observed in their comparative study arms, with a tendency toward better safety parameters at 48 weeks for the patients in the emtricitabine arm.

In those studies, when the researchers looked at the population of patients coinfected with HIV and HBV, similar safety parameters were again seen, with a tendency toward less elevation in liver function tests in the emtricitabine arm as compared to the comparative study arm.

In the emtricitabine study B-301, which was conducted in HBV-monoinfected patients, the incidence of adverse events for patients who took emtricitabine vs. placebo was also similar. Of a list of adverse events that occurred with a frequency of more than 5%, the percentage of patients who experienced at least 1 adverse event in the study was 84% in the emtricitabine group vs. 79% in the placebo group.

The overall conclusion of this presentation was that emtricitabine is safe for both HIV- and HBV-infected patients.

In my opinion, the position emtricitabine has in our treatment paradigm has been based mainly on data extrapolated from the very good safety and tolerability record of lamivudine in multiple clinical trials. Although this assumption has been accepted by most clinicians, it has been with some skepticism. However, now these studies present data that reassure us not only of the efficacy of emtricitabine in HIV- and HBV-infected patients, but about its safety and tolerability as well.