Dynamics of enfuvirtide resistance in HIV-infected patients during and after long-term enfuvirtide salvage therapy.
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.
Poveda
Eva
E
Department of Infectious Diseases, Hospital Carlos III, Madrid 28029, Spain.
Rodés
Berta
B
Lebel-Binay
Sophie
S
Faudon
Jean-Louis
JL
Jimenez
Victoria
V
Soriano
Vincent
V
D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D000077560:Enfuvirtide; D019143:Evolution, Molecular; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D016879:Salvage Therapy; D016415:Sequence Alignment; D013045:Species Specificity
D044966:Anti-Retroviral Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide