Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia

BACKGROUND: The T-20 vs. Optimized Regimen Only Study 2 (TORO 2) compared the efficacy and safety of 24 weeks of treatment with the fusion inhibitor enfuvirtide in combination with an optimized background antiretroviral regimen with the efficacy and safety of the optimized background regimen alone. METHODS: The patients had previous treatment with each of the three classes of antiretroviral drugs, documented resistance to each class, or both and a plasma level of human immunodeficiency virus type 1 (HIV-1) RNA of at least 5000 copies per milliliter. They were randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg twice daily) plus a background regimen optimized with the aid of resistance testing (enfuvirtide group) or the background regimen alone (control group). RESULTS: Of the 512 patients who underwent randomization, 335 in the enfuvirtide group and 169 in the control group received at least one dose of study medication and had at least one follow-up measurement of plasma HIV-1 RNA. The median base-line plasma HIV-1 RNA level was 5.1 log(sub 10) copies per milliliter in both groups. The median CD4+ cell count was 98.0 cells per cubic millimeter in the enfuvirtide group and 101.5 cells per cubic millimeter in the control group. Patients had a median of seven years of previous treatment and had received a median of 12 antiretroviral drugs. The background regimen comprised a mean of four antiretroviral drugs in both groups. At 24 weeks, the least-squares mean change from base line in the plasma viral load (intention-to-treat, last observation carried forward) was a decrease of 1.429 log(sub 10) copies per milliliter in the enfuvirtide group and a decrease of 0.648 log(sub 10) copies per milliliter in the control group, a difference of 0.781 log(sub 10) copies per milliliter (P<0.001). The mean increase in the CD4+ cell count was greater in the enfuvirtide group (65.5 cells per cubic millimeter) than in the control group (38.0 cells per cubic millimeter, P=0.02). CONCLUSIONS: The addition of enfuvirtide to an optimized background regimen provided significant viral suppression and immunologic benefit over a 24-week period in HIV-1-infected patients who had previously received multiple antiretroviral drugs.