Relationship between mutations in HIV-1 RNase H domain and nucleoside reverse transcriptase inhibitors resistance mutations in naïve and pre-treated HIV infected patients.
Recent studies have highlighted the need of investigating the in vivo role of ribonuclease H (RNase H) in nucleoside reverse transcriptase inhibitors (NRTIs) resistance. The prevalence of RNase H mutations in naive and in NRTI pre-treated patients in regimen failure were compared and some specific associations between NRTI resistance mutations and RNase H mutations were determined. Four positions were mutated more frequently in pre-treated patients than in naive patients: L469T/I/M/H, T470P/S/E/K, A554T/L/K, and K558R/G/E. Mutations at position K558 were also associated with the number of thymidine analog mutations (TAMs). These results suggest that these mutations could play a role in NRTI resistance.
Roquebert
Bénédicte
B
Department of Virology, Pitié-Salpêtrière Hospital and UPRES EA 2387, Université Pierre et Marie Curie, Paris, France.
Wirden
Marc
M
Simon
Anne
A
Deval
Jérome
J
Katlama
Christine
C
Calvez
Vincent
V
Marcelin
Anne-Geneviève
AG
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D021122:Protein Subunits / Q000187:drug effects / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D016914:Ribonuclease H / Q000187:drug effects / Q000235:genetics
D019380:Anti-HIV Agents; D021122:Protein Subunits; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H