title: N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations.
abstract: 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.
authors.affiliation: University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.forename: Katie
authors.initials: K
authors.lastname: Moore
authors.forename: Jessica
authors.initials: J
authors.lastname: Radzio
authors.forename: Secondo
authors.initials: S
authors.lastname: Sonza
authors.forename: Gilda
authors.initials: G
authors.lastname: Tachedjian
mesh_terms: 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
chemical_list: D009570:Nitriles; D063065:Organophosphonates; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine