Abstract: A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide (formerly called T-20) by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of supervised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.