Emtricitabine: a new nucleoside analogue for once-daily antiretroviral therapy

Highly active antiretroviral therapy has resulted in a dramatic decline in morbidity and mortality among patients infected with HIV. Nevertheless, this success has to be considered in the context of the current challenges and needs in this field. Adherence, toxicity, potency and resistance are still matters of intense research, which need to improve in order to overcome the current limitations of available drugs. Regarding needs, the improvement of convenience, tolerability and pharmacokinetics run in parallel with toxicity reduction, improvement of activity (both for wild-type and resistant virus), penetration into viral reservoirs and exploitation of new targets. The Food and Drug Administration approved erntricitabine in July 2003 for use in combination with other antiretroviral agents in adults with HIV-1 infection. Approval was based on the results of two Phase III clinical trials. The first was a double-blind study comparing the safety and efficacy of emtricitabine + didanosine + efavirenz to stavudine + didanosine + efavirenz as initial treatment in individuals who had not previously received antiretroviral therapy. At 24 and 48 weeks, patients receiving emtricitabine had significantly higher rates of virological suppression and greater increases in CD4+ counts than stavudine recipients. The second study was an open-label trial in treatment-experienced patients with HIV RNA < 400 copies/ml on a lamivudine-containing regimen in combination with either stavudine or zidovudine and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor for at least 12 weeks. Patients were randomised either to continue lamivudine (150 mg b.i.d.) or to switch to erntricitabine 200 mg o.d. while maintaining the same background medications. In this study, the proportion of patients whose viral loads remained suppressed at the < 400 and < 50 copies/ml levels were similar in the two treatment groups. Potency, tolerability, convenient dosing and a low rate of side effects are some of the main characteristics of this new drug.