Susceptibility of HIV-1 non-B subtypes and recombinant variants to Enfuvirtide.
BACKGROUND
Data on susceptibility of HIV-1 non-B subtypes to Enfuvirtide (ENF) is rather limited.


OBJECTIVE
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.


METHODS
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.


RESULTS
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 microg/ml was observed (range, 0.005-0.180 microg/ml). Natural polymorphisms, but not classical ENF resistance associated mutations within HR1 (residues 36-45) were identified in most non-B viruses.


CONCLUSIONS
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.
Holguín
Africa
A
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. aholguin.hciii@salud.madrid.org
Faudon
Jean Louis
JL
Labernardière
Jean-Louis
JL
Soriano
Vincent
V
D000328:Adult; D000595:Amino Acid Sequence; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D010802:Phylogeny
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide