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Dynamics of enfuvirtide resistance in HIV-infected patients during and after long-term enfuvirtide salvage therapy.

Poveda E, Rodés B, Lebel-Binay S, Faudon JL, Jimenez V, Soriano V

Department of Infectious Diseases, Hospital Carlos III, Madrid 28029, Spain.

Enfuvirtide (ENF) is the first of a novel class of drugs that blocks HIV fusion to host cells. We analyzed the dynamics of genotypic and phenotypic resistance to ENF during and after long-term ENF therapy and its clinical implications in eight heavily treatment-experienced HIV-infected patients who underwent salvage therapy with enfuvirtide along with other antiretroviral agents. All patients showed a rapid decline in plasma HIV-RNA followed by viral rebound. Changes at codons 36, 42, 43 and/or 44 within the HR1 region of gp41 were selected in all cases, resulting in high-level phenotypic resistance to ENF, ranging from 15- to 445-fold. Both genotypic and phenotypic resistance to ENF rapidly disappeared after discontinuation of the drug, suggesting that ENF-resistant viruses may have an impaired replicative capacity.

Published 15 November 2005 in J Clin Virol, 34(4): 295-301.
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