title: Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies.
abstract: OBJECTIVE
  Rilpivirine (RPV) is the latest approved nonnucleoside reverse transcriptase inhibitor (NNRTI). It displays in-vitro activity extending over other NNRTI-resistant HIV strains. There is scarce information about the rate of RPV resistance-associated mutations (RAMs) in patients failing other NNRTIs.
  
  
  METHODS
  RPV RAMs were examined in plasma samples collected from HIV patients that had recently failed NNRTI-based regimens at 22 clinics in Spain.
  
  
  RESULTS
  Resistance tests from a total of 1064 patients failing efavirenz (EFV) (54.5%), nevirapine (NVP) (40%) or etravirine (ETR) (5.5%) were examined. The prevalence of RPV RAMs was K101E (9.1%), K101P (1.4%), E138A (3.9%), E138G (0.3%), E138K (0.3%), E138Q (0.8%), V179L (0.2%), Y181C (21.8%), Y181I (0.5%), Y181V (0.2%), H221Y (8.3%), F227C (0.1%) and M230L (1.5%). K101E/M184I was seen in 1%. E138K/M184I were absent. Mutations L100I and V108I were significantly more frequent in patients failing EFV than NVP (7.9 vs. 0.2 and 12.2 vs. 7.3%, respectively). Conversely, Y181C, Y181I, V106A, H221Y and F227L were more prevalent following NVP than EFV failures. Using the Spanish resistance interpretation algorithm, 206 genotypes (19.3%) from patients failing NNRTI (NVP 52%, EFV 40.8% and ETR 7.8%) were considered as RPV resistant. In patients with ETR failure, cross-resistance to RPV was seen in 27.6%, mainly as result of Y181C (81.3%), V179I (43.8%), V90I (31.3%) and V108I (18.8%).
  
  
  CONCLUSIONS
  RPV resistance is overall recognized in nearly 20% of patients failing other NNRTIs. It is more common following ETR (27.6%) or NVP (25%) failures than EFV (14.5%). E138 mutants are rarely seen in this context.
authors: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. lourdes.anta@hotmail.es
authors: Lourdes
authors: L
authors: Anta
authors: Josep M
authors: JM
authors: Llibre
authors: Eva
authors: E
authors: Poveda
authors: José L
authors: JL
authors: Blanco
authors: Marta
authors: M
authors: Alvarez
authors: María J
authors: MJ
authors: Pérez-Elías
authors: Antonio
authors: A
authors: Aguilera
authors: Estrella
authors: E
authors: Caballero
authors: Vicente
authors: V
authors: Soriano
authors: Carmen
authors: C
authors: de Mendoza
mesh_terms: D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D009705:Nucleosides / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000068696:Rilpivirine; D013030:Spain / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D009705:Nucleosides; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine