Format

Send to

Choose Destination
AIDS. 2004 Sep 3;18(13):1787-94.

Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on-treatment HIV-1 isolates.

Author information

1
Trimeris Inc. Durham, North Carolina, Roche Biosciences, Palo Alto, California, USA.

Abstract

BACKGROUND:

Enfuvirtide (ENF) is the first of a novel class of drugs that block HIV gp41-mediated viral fusion to host cells. Viruses with mutations at positions 36-38 in HIV-1 gp41 and/or reduced susceptibility to ENF have been selected both in vitro and in vivo.

METHODS:

An analysis of baseline and on-treatment ENF susceptibility in virus samples from Phase II clinical trial patients treated with ENF as functional monotherapy for 28 days (TRI-003) or in combination with oral antiretrovirals for >/= 48 weeks (T20-205, T20-206 and T20-208). Population sequencing identified amino acid (aa) substitutions at positions 36-45 of gp41 in plasma HIV-1. ENF susceptibility of virus isolates was tested in the cMAGI assay and viral DNA was sequenced for selected isolates.

RESULTS:

HIV-1 gp41 aa 36-45 were highly conserved in virus from ENF-naive patients, except for a 15% incidence of N42S which did not reduce sensitivity to ENF. Virus from patients experiencing viral load rebound exhibited reduced susceptibility to ENF and substitutions in gp41 aa 36-45. The most common substitutions observed on treatment were at positions 36, 38, 40, 42 and 43. On-treatment changes in the phenotypic susceptibility of virus isolates to ENF were generally associated with genotypic changes in aa 36-45. There was a relatively lower incidence of ENF resistance in patients with baseline sensitivity to more oral antiretrovirals in comparison to patients sensitive to fewer antiretrovirals.

CONCLUSIONS:

These data identify the importance of HIV-1 gp41 aa 36-45 in the emergence of resistance to ENF.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center