Evolution of genotypic resistance to enfuvirtide in HIV-1 isolates from different group M subtypes

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology (Impact Factor: 3.47). 03/2009; 44(4):325-8. DOI: 10.1016/j.jcv.2009.01.012
Source: PubMed

ABSTRACT Enfuvirtide is active against isolates from different HIV-1 subtypes. In vitro and in vivo studies reveal that resistance mutations are primarily found within the region spanning amino acid 36-45 of gp41. However, most studies include only subtype B strains, while it is known that especially the env region is very divergent among subtypes.
To analyze the gp41 HR1 genetic evolution during failure of enfuvirtide-containing salvage regimens in 19 HIV-1 patients infected with strains from different group M subtypes.
The gp41 sequence was determined at baseline and upon failure in 19 patients. For a subset of 7 patients, samples were available after discontinuation of enfuvirtide.
Our results confirmed the conserved nature of the HR1 region. Escape mutants during chronic treatment with enfuvirtide were mainly observed within region 36-45. One novel mutation was identified, i.e. S42G in a subtype A1 strain.
Different subtypes escape enfuvirtide selective pressure through similar mutational patterns, however a new S42G variant was observed. The in vivo selection of S42G suggests that it might play a role in enfuvirtide resistance. Therefore, it could be considered as a candidate mutation to be included within drug resistance interpretation systems.

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