N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations.
We previously demonstrated that N348I in HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, both of these inhibitors are currently infrequently used in developed countries, and the impact of N348I on newer reverse transcriptase inhibitors, such as tenofovir and etravirine, is unknown. In this study, we demonstrate that N348I alone confers no resistance to tenofovir and low-level resistance to etravirine. However, N348I significantly decreases tenofovir susceptibility when combined with thymidine analogue mutations and etravirine susceptibility when combined with Y181C.
Sluis-Cremer
Nicolas
N
University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA, USA.
Moore
Katie
K
Radzio
Jessica
J
Sonza
Secondo
S
Tachedjian
Gilda
G
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D016297:Mutagenesis, Site-Directed / Q000379:methods; D009154:Mutation / Q000235:genetics*; D009570:Nitriles; D063065:Organophosphonates / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir
D009570:Nitriles; D063065:Organophosphonates; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine