Dynamics of raltegravir resistance profile in an HIV type 2-infected patient.
The evolutionary dynamics of RAL resistance in the HIV-2 virus were examined through population and clonal sequence analysis of the IN from baseline, during treatment, and after stopping RAL therapy. The treatment failure of an RAL regimen in the HIV-2 patient studied was associated with the emergence of mutations via the N155H resistance pathway and subsequent switching to the Y143C mutational route. This study has also identified four novel secondary mutations, Q91R, S147G, A153G, and M183I, not previously reported in HIV-1 patients failing RAL therapy. Resistant variants involving the Y143C pathway were noted to have persisted beyond 4 weeks following the cessation of RAL therapy. All resistance-associated mutations were lost at 20 weeks after stopping RAL therapy. Our findings provide evidence supporting the supposition that substantial cross-resistance between strand transfer IN-Is is likely in HIV-2 as shown in HIV-1.
Xu
Li
L
Health Protection Agency, Heart of England NHS Foundation Trust , Birmingham B9 5SS, UK. l.mccrae@bham.ac.uk
Anderson
Jane
J
Garrett
Nigel
N
Ferns
Bridget
B
Wildfire
Adrian
A
Cook
Pamela
P
Workman
Judith
J
Graham
Susan
S
Smit
Erasmus
E
D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D019427:HIV Integrase / Q000032:analysis / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D000068898:Raltegravir Potassium; D017423:Sequence Analysis, RNA; D017211:Treatment Failure
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019427:HIV Integrase