 At steady-state concentrations, the mean blood plasma half-life t12 of tenofovir and emtricitabine are 15.9 hours and 10.7 hours, respectively. 4 However, the intracellular t12 of tenofovir diphosphate and emtricitabine triphosphate are 60 hours and 39 hours, respectively.5 The long intracellular t12 of the active forms of these drugs might hold advantages for episodic dosing. However, the long t12 might also hold disadvantages in terms of the development of viral resistance mutations. This phenomenon the development of resistance after a single dose of a long t12 drug, has been previously seen with nevirapine given during delivery to HIV-infected women to prevent mother to child transmission of HIV.6 However, these women were chronically infected, rather than newly infected, as would be the case with populations exposed to prevention strategies. 