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. J. Med. Virol. 79:207–211, 2007. © 2007 Wiley-Liss, Inc.