title: Transmitted drug resistance to rilpivirine among antiretroviral-naïve patients living with HIV from northern Poland.
abstract: BACKGROUND
  Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naïve individuals with HIV-1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV-associated drug resistance mutations was assessed in this study.
  
  
  METHODS
  For the study, 244 viral genome sequences from antiretroviral-naïve individuals were obtained by bulk sequencing. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data.
  
  
  RESULTS
  IAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent.
  
  
  CONCLUSIONS
  Prevalence of RPV-associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non-B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV-naïve patients; however, genotype resistance testing should remain compulsory before starting an RPV-based regimen.
authors.affiliation: Department of Infectious Diseases, Hepatology and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland; mparczewski@yahoo.co.uk.
authors.forename: Miłosz
authors.initials: M
authors.lastname: Parczewski
authors.affiliation: Department of Infectious Diseases, Hepatology and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Urbańska
authors.affiliation: Department of Infectious Diseases, Hepatology and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maciejewska
authors.affiliation: Department of Infectious Diseases, Hepatology and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Witak-Jȩdra
authors.affiliation: Department of Infectious Diseases, Hepatology and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leszczyszyn-Pynka
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009570:Nitriles / Q000627:therapeutic use*; D011044:Poland / Q000453:epidemiology; D015995:Prevalence; D011743:Pyrimidines / Q000627:therapeutic use*; D000068696:Rilpivirine
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D000068696:Rilpivirine
keywords: HIV-1 non-B variants; NNRTI; drug resistance; rilpivirine; sequencing; transmission
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