title: Prevalence of etravirine resistance associated mutations in HIV-1 strains isolated from infected individuals failing efavirenz: comparison between subtype B and non-B genetic variants.
abstract: Etravirine (ETR) is a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) with a high genetic barrier to the development of resistance and with potential activity against Human immunodeficiency virus type 1 (HIV-1) strains resistant to first-generation NNRTIs. The objective of this study was to investigate the prevalence of ETR resistance associated mutations (RAMs) in HIV-1 strains isolated from infected individuals failing efavirenz (EFV), as well as to evaluate possible differences in the distribution of ETR RAMs between subtype B and non-B genetic variants. Nucleotide sequences of the protease and partial reverse transcriptase (RT) coding regions of the pol gene of 55 HIV-1 strains isolated from infected individuals failing EFV on regular follow-up at a reference center in Portugal, were retrospectively analyzed. The most prevalent ETR RAMs observed were L100I, V90I, and K101E, with a prevalence of 16.4% (n = 9), 9.1% (n = 5), and 5.5% (n = 3), respectively. Overall, 47.3% (n = 26) of the nucleotide sequences had at least one ETR RAM: 38.2% (n = 21) had one ETR RAM, 7.3% (n = 4) had two ETR RAMs and 1.8% (n = 1) had three ETR RAMs. No statistically significant differences were found in the distribution of ETR RAMs between subtype B and non-B genetic variants. The results demonstrate that ETR rescue therapy is a viable option in treatment-experienced individuals failing EFV and suggests that ETR may be equally useful in HIV-1 infections caused by different genetic variants.
authors.affiliation: Laboratory of Virology, Coimbra University Hospitals, Coimbra, Portugal. joaovaz@huc.min-saude.pt
authors.forename: João
authors.initials: J
authors.lastname: Pereira-Vaz
authors.forename: Vitor
authors.initials: V
authors.lastname: Duque
authors.forename: Branca
authors.initials: B
authors.lastname: Pereira
authors.forename: Vanda
authors.initials: V
authors.lastname: Mota
authors.forename: Célia
authors.initials: C
authors.lastname: Morais
authors.forename: José
authors.initials: J
authors.lastname: Saraiva-da-Cunha
authors.forename: António
authors.initials: A
authors.lastname: Meliço-Silvestre
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D009570:Nitriles; D011174:Portugal; D015995:Prevalence; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D050505:Mutant Proteins; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C098320:efavirenz