Emtricitabine was approved by the FDA in July 2003 for use in combination with other antiretroviral agents in adults with HIV infection. In 2005, it was approved for use in pediatric patients. Initial approval was based on the results of 2 Phase III clinical trials. A double-blind study compared emtricitabine + didanosine + efavirenz with 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 virologic suppression than did stavudine recipients.(1)

An open-label trial of treatment-experienced patients with HIV RNA <400 copies/mL on a lamivudine-containing regimen randomized patients either to continue lamivudine or to switch to once-daily emtricitabine, in combination with either stavudine or zidovudine and either a protease inhibitor or an NNRTI. The proportion of patients whose viral loads remained suppressed at the <400 copies/mL and <50 copies/mL level were similar in the two treatment groups.(2)

Emtricitabine is available in capsules and oral solution. Emtricitabine is available in combination with tenofovir as a single tablet (Truvada). Emtricitabine is also available in combination with tenofovir and efavirenz as a single tablet (Atripla).

Dosing of Emtricitabine Adult 200 mg QD Pediatric <3 months Not approved ≥3 months 6 mg/kg QD, maximum 240 mg QD Children >33 kg and able to swallow capsules 200 mg QD

Key to abbreviations: QD, once daily.

		There are no food restrictions.

		Dosage adjustment is recommended in renal insufficiency.

		Please consult product labeling for detailed dosing information.

		FDA Pregnancy Category B.

Regimens containing emtricitabine in combination with other antiretroviral medications have been shown to achieve effective viral suppression in initial therapy (see "Use in Initial vs Subsequent Therapy"). Emtricitabine does not appear to interact significantly with enzymes involved in drug metabolism. Clinically significant drug-drug interactions involving emtricitabine have not been identified.(3)

Emricitabine and lamivudine have no significant additive potency and share nearly identical resistance profiles; they should not be used together.

Treatment guidelines of the U.S. Department of Health and Human Services include emtricitabine in each "preferred" and "alternative" dual-nucleoside backbone for initial combination therapy. The guidelines also state that lamivudine may be used in place of emtricitabine and vice versa.

Used in initial treatment, emtricitabine appears to compare favorably with stavudine and with lamivudine. In one licensing study (see "Approval"), recipients of emtricitabine (dosed daily) were more likely than recipients of stavudine (dosed twice daily) to achieve viral loads <50 copies/mL at 48 weeks in an intent-to-treat analysis (78% for emtricitabine vs 59% for lamivudine, p < .001).(1) Those receiving emtricitabine also had greater increases in CD4 cells at 48 weeks (mean increase 168 cells/µL versus 134 cells/µL, but this difference was not statistically significant [p = .15]).(1) A randomized, double-blind study of initial treatment comparing emtricitabine (dosed daily) with lamivudine (dosed twice daily), each combined with stavudine and either nevirapine or efavirenz, showed similar rates of virologic failure at 48 weeks (Kaplan-Meier probability of virologic failure: 16% for emtricitabine vs 11% for lamivudine; p value not significant).(2)

Few data are available on the use of emtricitabine in treatment of individuals who have experienced virologic failure on an initial regimen. Because the mutations associated with resistance to emtricitabine are largely identical to those conferring resistance to lamivudine (see "Resistance"), it is unlikely that emtricitabine will be of benefit to patients changing treatment because of lamivudine resistance.

Studies of treated individuals with viral load ≤400 copies/mL on treatment have found that switching to emtricitabine-containing regimens does not adversely affect viral suppression in patients on regimens containing lamivudine (2,4) or a protease inhibitor.(5)

Symptomatic side effects of emtricitabine may be difficult to distinguish from those of other antiretrovirals with which it is combined. The most common adverse effects noted in clinical trials of emtricitabine with other antiviral agents were headache, diarrhea, nausea, and rash. Side effects were seldom severe, with approximately 1% of participants discontinuing participation because of these events. Skin discoloration, manifested by hyperpigmentation of the palms or soles, or both, and generally mild and asymptomatic, has been associated with emtricitabine.(3)

Nucleoside analogues may be associated with mitochondrial toxicity leading to potentially serious long-term side effects such as lactic acidosis and disorders of lipid metabolism,(6) but the extent to which emtricitabine may contribute to such effects is not known.

Resistance to emtricitabine may develop with only a single viral mutation in the setting of suboptimal viral suppression. It is therefore essential to emphasize patient adherence, to assess motivation, and to discuss possible side effects and strategies for their management before any regimen containing emtricitabine is initiated.

Resistance to emtricitabine, as with resistance to lamivudine, is most frequently associated with the selection of a mutation at codon 184, although in one study no such mutation was detectable in the majority of individuals experiencing viral recurrence on a regimen containing emtricitabine.(7)

To avoid long-term treatment failure resulting from resistance, emtricitabine should be used only in regimens that are expected to be fully suppressive of viral replication.

Implications of emtricitabine resistance for treatment with other antiretrovirals

HIV isolates with resistance to emtricitabine by virtue of a mutation at codon 184 have been shown to be cross-resistant to lamivudine, but retained sensitivity to abacavir, didanosine, stavudine, tenofovir, and zidovudine.(3)

Implications of resistance to other antiretrovirals for treatment with emtricitabine

HIV strains harboring mutations conferring reduced susceptibility to stavudine and zidovudine (at codons 41, 67, 70, 210, 215, or 219) or didanosine (codon 74) have been found to remain sensitive to emtricitabine.(3)

Emtricitabine is active against hepatitis B virus,(8,9) but is not currently approved for treatment of hepatitis B infection. Few data are available on the safety and efficacy of emtricitabine in patients coinfected with HIV and hepatitis B.(10) Exacerbation of hepatitis B has been reported in patients after discontinuation of emtricitabine.(3)