Susceptibility of HIV-1 non-B subtypes and recombinant variants to Enfuvirtide

• Published in: Journal of clinical virology Vol. 38; no. 2; pp. 176 - 180
• Main Authors: Holguín, Africa, Faudon, Jean Louis, Labernardière, Jean-Louis, Soriano, Vincent
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.02.2007; Elsevier Science
• Subjects: Adult; Allergy and Immunology; Amino Acid Sequence; Biological and medical sciences; Drug resistance; Enfuvirtide; Female; Fundamental and applied biological sciences. Psychology; Gp41; HIV Envelope Protein gp41 - genetics; HIV Envelope Protein gp41 - immunology; HIV Envelope Protein gp41 - pharmacology; HIV Fusion Inhibitors - pharmacology; HIV Infections - virology; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious Disease; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Peptide Fragments - pharmacology; Phylogeny; Subtypes; Viral diseases; Virology; HIV-1; Subtypes; Enfuvirtide; Drug resistance; Gp41; Microbiology; HIV-1 virus; Retroviridae; Lentivirus; Virology; Virus; Resistance; Sensitivity; Human immunodeficiency virus; Subtype
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2006.09.002

Data on susceptibility of HIV-1 non-B subtypes to Enfuvirtide (ENF) is rather limited. To determine if ENF could be active in vitro against HIV-1 non-B subtypes and how the gp41 genetic variability across variants may influence ENF susceptibility. Using PHENOSCRIPT ® Env, a recombinant envelope virus assay, ENF susceptibility was investigated in isolates from 19 drug-naive HIV-1-infected individuals harboring non-B subtypes. Using phylogenetic analyses of the gp41 gene, distinct HIV-1 subtypes were recognized: A (2), C (5), D (1), F (2), G (1), J (1), CRF02_AG (6) and CRF06 (1). Susceptibility to ENF and IC 50 values in vitro could be obtained in only 13 (68.4%) specimens, most likely due to the high genetic variability in HR1 and HR2 regions in the remaining cases. A wide range of IC 50 values with a median of 0.013 μg/ml was observed (range, 0.005–0.180 μg/ml). Natural polymorphisms, but not classical ENF resistance associated mutations within HR1 (residues 36–45) were identified in most non-B viruses. This study provides information about the baseline susceptibility to ENF in antiretroviral-naive subjects infected with different HIV-1 non-B subtypes. Susceptibility to ENF seems to be preserved despite high genetic variability in HR1 and HR2 regions.