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

• Published in: Journal of clinical virology 2009-04, Vol.44 (4), p.325-328
• Main Authors: Covens, Kris, Kabeya, Kabamba, Schrooten, Yoeri, Dekeersmaeker, Nathalie, Van Wijngaerden, Eric, Vandamme, Anne-Mieke, De Wit, Stéphane, Van Laethem, Kristel
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Amino Acid Sequence; Amino Acid Substitution - genetics; Anti-HIV Agents - pharmacology; Biological and medical sciences; Drug Resistance, Viral; Enfuvirtide; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; HIV Envelope Protein gp41 - genetics; HIV Envelope Protein gp41 - pharmacology; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - classification; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human viral diseases; Humans; Infectious Disease; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation, Missense; Peptide Fragments - pharmacology; Resistance development; Salvage Therapy - methods; Sequence Analysis, DNA; Subtypes; Treatment Failure; Viral diseases; Virology
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2009.01.012

Abstract Background 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. Objectives 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. Study design 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. Results 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. Conclusions 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.