[Clinical efficacy and tolerance of enfuvirtide (Fuzeon), new antiretroviral inhibitors of intracellular penetration of human immunodeficiency virus (HIV) type 1].

The TORO 1 and TORO 2 clinical trials compared the efficacy and safety of enfuvirtide in combination with an optimized background antiretroviral regimen and optimized background regimen alone in HIV-1 infected patients. The patients had had previous treatment with each of the three classes of antiretroviral drugs and had a plasma level of HIV-1 RNA above 5000 copies/ml at baseline. They were randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg subcutaneously twice daily) plus a background regimen optimized with the aid of resistance testing, or an optimized antiretroviral regimen alone (control group). Six hundred and sixty-one patients were enrolled in the enfuvirtide arm and 334 in the control group. The median baseline plasma HIV-1 RNA level was 5.2 log10 copies/ml in the enfuvirtide group and 5.1 log10 copies/ml in the control group. Patients had a median of 7 years of previous antiretroviral treatment. The optimized background regimen comprised a mean of 4 antiretroviral drugs in both groups. At week 48, the mean reduction in viral load was -1.48 log10 copies/ml in the enfuvirtide group, and -0.63 log10 copies/ml in the control group (difference = 0.846 log10 copies/ml, IC95%: -1.066; -0.626. p < 0.0001). The mean increase in the CD4+ cell count was significantly greater in the enfuvirtide group (91 cells/mm3) than in the control group (45 cells/mm3). Injection site reactions were the main reported adverse event which occurred in 98% of the enfuvirtide patients. Most had mild to moderate pain or discomfort not requiring analgesic or limiting usual activities.