In combination with other antiretroviral drugs, enfuvirtide is indicated in the treatment of HIV-1 patients, exposed or with failure to previous therapy with at least one of each of the three antiretroviral drugs classes (nucleoside inhibitors, non nucleoside inhibitors and protease inhibitors) or intolerant to these therapies. Genotypic resistance tests are helpful to evaluate acquired resistance to individual drugs, to select the remaining active drugs and to eliminate from the background regimen those with characterized resistance. In patients receiving enfuvirtide plus an optimized background regimen, the best results are reported in those with a baseline CD4+ count above 100/mm3, a plasma viral load below 100000 copies/ml, having been previously treated with less than 10 antiretroviral drugs and having at least 2 active drugs in their background regimen. Patients combining these 4 criteria have an 80% chance to have a plasma viral load below 400 copies/ml after a 24 weeks course of therapy. In terms of Quality of Life, studies demonstrated that patients treated with enfuvirtide have improvement in many measures of health-related quality of life, comparatively to those receiving the optimized therapy alone.