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Resistance to enfuvirtide is associated with mutations in the HR1 and HR2 subunits of the envelope glycoprotein (gp)41, most notably amino acids 36–45 of HR1. In vitro studies using side-directed mutagenesis have indicated that many of the HR1 mutations associated with enfuvirtide resistance significantly reduce the ability of the virus to replicate. However, until now, no in vivo studies had been conducted to confirm this observation.
In the present study, investigators evaluated seven patients with multidrug-resistant virus who received enfuvirtide for more than 3 years but did not achieve virologic control. Genotypes, phenotypes, and replicative capacity were measured before and after failure of enfuvirtide therapy.
Pretherapy susceptibili…