HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.
BACKGROUND
Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.


METHODS
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.


RESULTS
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.


CONCLUSIONS
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.
Bar-Magen
Tamara
T
McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Canada.
Donahue
Daniel A
DA
McDonough
Emily I
EI
Kuhl
Björn D
BD
Faltenbacher
Verena H
VH
Xu
Hongtao
H
Michaud
Veronique
V
Sloan
Richard D
RD
Wainberg
Mark A
MA
D002478:Cells, Cultured; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1