Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.
Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. Our findings illustrate the ability of HIV-1 to escape from suboptimal antiretroviral drug pressure through selection of pre-existing drug-resistant mutants, underscoring the importance of using fully active antiretroviral regimens to treat all HIV-1-infected subjects.
Codoñer
Francisco M
FM
HIVACAT, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Pou
Christian
C
Thielen
Alexander
A
García
Federico
F
Delgado
Rafael
R
Dalmau
David
D
Santos
José Ramon
JR
Buzón
Maria José
MJ
Martínez-Picado
Javier
J
Alvarez-Tejado
Miguel
M
Clotet
Bonaventura
B
Ruiz
Lidia
L
Paredes
Roger
R
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012641:Selection, Genetic / Q000187:drug effects; D017211:Treatment Failure
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase