Enfuvirtide (ENF/T-20), the first FDA approved HIV-1 fusion inhibitor, exhibits both high efficacy and low toxicity. However, due to the emergence of resistance to ENF, treatment strategies involving ENF interruption to allow drug sensitive virus to grow, followed by ENF re-administration have been examined. In this talk, I will present a mathematical model to study the dynamics of plasma viral RNA level and the competition between ENF-sensitive and ENF-resistant viruses during ENF interruption and ENF re-administration. Our result accounts for the increased CD4+ T cell count observed during ENF re-administration in the absence of viral load decrease. We found that the plasma viral RNA level does not depend upon the fitness cost of the resistant virus or the drug efficacy, but does depend on a number of other viral dynamic parameters. The combined effect of the fitness loss of ENF-resistant virus and its initial proportion are the main factors determining the dominance of the drug sensitive virus population during ENF interruption, while the efficacy of ENF against ENF-resistant viruses also plays a role in determining the dominance of the virus population during ENF re-administration.