A cohort study of enfuvirtide immunological and virological efficacy in clinical practice.

The aim of the study was to evaluate, under routine circumstances, the immunological and virological efficacy of antiretroviral regimens containing enfuvirtide in multi-class experienced HIV-1 infected patients. This retrospective monocentric study analyzed the clinical, immunological, and virological data of 18 HIV-1 infected patients who started enfuvirtide and completed at least 3 months of therapy. Following 3 months of enfuvirtide therapy, 11 (61%) patients had HIV-1 RNA below 400 copies/ml, among whom 8 (44%) patients below 50 copies/ml. In the ten patients still receiving enfuvirtide after 12 months, the median increase in CD4 cell count was 159 cells/microl (range, -25 to +301) and the mean decrease in HIV-1 RNA was 2.5 +/- 1.4 log(10) copies/ml; in six of these patients, viral load remained below 50 copies/ml. Five patients discontinued enfuvirtide for virological failure but none as a consequence of adverse event. Mutations located within the 36-45 amino acid domain of HR1 region of gp41 and associated to enfuvirtide resistance were found in all seven patients with persistent viral replication. In addition, a new mutation, A50V, emerged in one patient with late viral rebound. Its disappearance after treatment discontinuation suggests that it could play a role in resistance to enfuvirtide. In conclusion, enfuvirtide may be a good therapeutic option as rescue therapy in treatment-experienced patients. However, the mutations conferring resistance to enfuvirtide develop rapidly when viral load is not controlled confirming that enfuvirtide should be prescribed in association with an active background regimen.